Apparatus for integrated process of magnetic particles and method of controlling the same

ABSTRACT

The present invention relates to an apparatus for an integrated process of magnetic particles and a method of controlling the same, for executing a process for magnetic particles incorporated in a fluid in an integrated state. The present invention aims to provide an apparatus for an integrated process of magnetic particles and a method of controlling the same, that can promptly and efficiently process all together in high precision, with the process of magnetic particles integrated. 
     The apparatus for an integrated process of magnetic particles comprises a reservoir body provided with plural pit-like reservoirs for storing a drawn liquid arranged in a matrix, a sliding body with jutting plural sliding projections sliding through the reservoirs and capable of moving vertically to and from the reservoir body, plural nozzles attached to the lower parts of the reservoirs and capable of passing the liquid therethrough, a magnetic force device capable of magnetization and demagnetization having plural through sections in which is inserted each nozzle and having a wall part in contact with or near the outer side surface of the nozzle, with the nozzles inserted thereinto, wherein each wall part has two divided wall parts being apart from one another in such a manner that the divided wall parts have opposite polarities by magnetization, respectively.

FIELD OF THE INVENTION

The present invention relates to an apparatus for an integrated processof magnetic particles and a method of controlling the same.Particularly, the present invention relates to an apparatus for anintegrated process of magnetic particles and a method of controlling thesame, which can execute processes such as reaction, separation, fixingquantity, dispensation, clarification, concentration, agitation,suspension, dilution, and operations such as observation, extraction,recovery, isolation, and indications in regard to for example, immunesubstances such as antibodies or antigens, genetic substances (DNA, RNA,m-RNA and so on), bacillus, and other useful substances such asmedicines, or target substances, for medical treatment, inspection,diagnosis, medical care, research, quantitative analysis, qualitativeanalysis and so on in all manner of fields such as medical science,agricultural science, engineering, scientific fields, pharmaceuticals,by using a fluid incorporating magnetic particles and capable of beingprocessed in large numbers in a vessel such as a microplate.

BACKGROUND OF THE INVENTION

Currently, there is a pipette device shown in FIG. 21. As shown in thisview, the pipette device has a magnet driving device for controlling todrive a magnetic source M and a holding body V The magnetic source Mhaving a magnet section and the holding body V having a holding section,are rotatably mounted in an up-down mechanism of the pipette device insuch a manner that they can approach and go away from one another.

When the up-down mechanism O moves vertically, as shown in FIG. 21, themagnetic source M and the holding body V move in obedience to movementof rollers R_(A) R_(B) of the up-down mechanism O so that they close ina way that they hold a tip between them. As a result, the magneticsource M and the holding body V can simultaneously come in contact withthe pipette tip T in a manner that they hold the pipette tip T, and themagnetic source M can surely approach to the tip T and separate from thetip T.

In order to execute a process for large numbers of substances such ascombinatorial chemistry, DNA function analysis, or automatic measurementof immune substances, many pipette tips are necessary. Currently, amultiplex pipette device having many pipette tips arranged in a line isused, as shown in FIG. 22. In regard to the conventional pipette devicecapable of processing magnetic particles, not only pipette tips but alsomechanisms (M₁, M₂, M₃, M₄, V₁, V₂, V₃, V₄) which are mounted per eachpipette tip for applying and removing a magnetic field to and from thepipette tip respectively by driving a magnet, need to be multiplyprovided and linked.

Therefore, though such a multi-linking using tips arranged in a line isembodied, such an integration as applying al magnetic filed to manylines of nozzles simultaneously by using the device causes the problemthat the apparatus is scaled up in size and processes cannot be executedin an integrated state.

Particularly, when a large number of samples are handled and the wells(plate holes of a microplate) of a vessel are for example, 96 wells or384 wells or more, driving sections for applying and removing themagnetic field to and from the nozzles and magnetic particles, need beintegrated in high density. However, since the driving section preventsintegration, there is a problem that the process for magnetic substancescannot be integrated.

The present invention aims to resolve the aforementioned problems. Afirst object of the invention is to provide an apparatus for anintegrated process of magnetic particles and a method of controlling thesame, that can promptly and efficiently process all together in high,precision, with integration of the process of magnetic particles, byintegrating nozzles and sections for driving sections for applying themagnetic fields to the nozzles.

A second object of the invention is to provide an apparatus for anintegrated process of magnetic particles and a method of controlling thesame, which integrates the process for the magnetic particles withoutusing a magnet driving device having elements whose scale or actionrange is large, and which can execute the process of a large number ofsubstances with a small scale and compact device.

A third object of the invention is to provide an apparatus for anintegrated process of magnetic particles and a method of controlling thesame, in which a plurality of elements are integrated, the structure ofelements per unit of integration is simplified and the cost performanceis high.

A fourth object of the invention is to provide an apparatus for anintegrated process of magnetic particles and a method of controlling thesame, which is suitable for a microplate having a plurality of wells,and which has such diversity and flexibility that it can be applied tovarious fields requiring processes for large numbers of substances suchas combinatory chemistry, DNA function analysis, and automaticmeasurement of immune substances, and has diversity and flexibility.

A fifth object of the invention is to provide an apparatus for anintegrated process of magnetic particles and a method of controlling thesame, which can exclude human operations to the utmost and facilitatesautomatization, in a process for fluids.

A sixth object of the invention is to provide an apparatus for anintegrated process of magnetic particles and a method of controlling thesame, which can exclude mechanical movement to the utmost, can work at alow running cost, has a long life span, and is easily handled.

A seventh object of the invention is to provide an apparatus for anintegrated process of magnetic particles and a method of controlling thesame, which can complete whole steps within a confined space and canexclude influence between the space and the outer environment to theutmost, and which can reliably execute the process.

SUMMARY OF THE INVENTION

In order to resolve the above technical problems, a first aspect of theinvention is an apparatus which comprises a drawing/discharging devicefor drawing and discharging a fluid, plural nozzles for passing thefluid therethrough while drawing and discharging, and a magnetic forcedevice for applying and removing a magnetic field to and from thenozzles respectively with remaining stationary near each nozzleexterior.

The “drawing/discharging device” comprises for example, a plurality ofseparate cylindrical containers being bundled, or a block in whichplural cylindrical containers are formed. Each container comprises forexample, a drawing/discharging line, a plunger, an elastic body, bellowsor a diaphragm, for drawing and discharging a fluid. “Fluid” includes aliquid and a gas. It also includes a fluid incorporating or suspendingsolid substances such as magnetic particles or magnetic substances.

“Plural nozzles” are preferably arranged in a plane-like state forconvenience sake, in which for example, a matrix-like state, a circularstate and a two-dimensional state are included, but the plane-like stateis not restricted to these examples.

“Nozzle” may be fixed to the drawing/discharging device, or may comprisea pipette tip that is detachably mounted to the drawing/dischargingdevice directly or to a section fixed to the drawing/discharging device.

The pipette tip includes a disposable type and a cleaning and arecycling type. “Magnetic force device” serves to make the magneticsubstances or magnetic particles suspended or incorporated in a liquidadhere to inner walls of the nozzles. Thus, a process for magneticparticles such as transferring, agitation, cleaning, separation,resuspension and so on can be executed. “Magnetic force device” is onethat can simultaneously apply and remove a magnetic field to and fromthe nozzles respectively, in a manner that the neighborhood of the outerside of the nozzles remains stationary. The structure does not require acomplicated mechanism near the outer side of the nozzles or a space formovement. Therefore, a plurality of nozzles can be densely integrated,instead. Hence, the process for the magnetic particles can beintegrated, the apparatus can be scaled down, the space can be reduced,and the process can be efficiently executed. Furthermore, since largenumbers of small quantity objects can have conditions being equal anduniform in time and space, the process for each small quantity objectcan be executed in high precision. Since a large number of smallquantity objects can be simultaneously processed, the process can besped up and efficiency of the process can increase.

Here, since neighborhood of “each nozzle exterior” remains stationary,the case where a moving mechanism for applying and removing the magneticfield, is mounted at a part outside of the neighborhood of the nozzleexterior is not excluded. Furthermore, the case where the magnetic forcedevice moves not for the purpose of applying and removing the magneticfield, but for transportation of the entire apparatus, is not excluded.

The magnetic force device is constructed, for instance, so that a partof each nozzle or nozzle outer member is made of a magnetic materialsuch as a para-magnetic material or a super para-magnetic material etc.which is magnetically connected to an electromagnet having a switch, ora magnetic source such as permanent magnet or electromagnet capable ofdetaching therefrom.

“Magnetic particles or magnetic substances” are processed so as to beable to combine with related substances such as target substances. Themagnetic particles have a size of for example, about 0.1-100 μm, andcombine with the related substances by holding the related substances ina porous material having a plurality of recesses in the magneticparticles, by adsorbing the related substances, or by reacting therelated substances with substances coated or held in the magneticparticles. For example, the magnetic particles are made of a superpara-magnetic substance. Furthermore, the magnetic force device may befixed to the drawing/discharging device, or may be detachably mounted.

A second aspect of the invention is an apparatus for an integratedprocess of magnetic particles according to the first aspect of theinvention, wherein the magnetic force device can apply and remove themagnetic force to and from the nozzles respectively by enablingmagnetization and demagnetization in a nozzle outer member brought incontact with or being near the outer surface of the nozzle or at least apart of the nozzle, with remaining stationary near each nozzle exterior.

“Magnetization and demagnetization” implies that the magnetic materialis magnetized under influence of the magnetic field and demagnetizedwithout influence of the magnetic field.

With the present invention, since the magnetic force device can besimplified in structure, the structure of the entire apparatus can besimplified and the cost of the products can be reduced. Particularly, inthe case of “enabling magnetization and demagnetization in at least partof the nozzle”, since the necessary volume or the bottom area formagnetization and demagnetization is small, integration is improved muchmore.

A third aspect of the invention is an apparatus for an integratedprocess of magnetic particles according to the second aspect of theinvention, wherein the magnetic force device comprises a magnetic membermade of a magnetic material and provided with a plurality of throughsections capable of taking insertion of nozzles, wherein the nozzleouter member is a wall of the through sections. With the presentinvention, a plurality of nozzles can be easily and densely integratedby a simple structure. Consequently, the cost of products can bereduced, and the apparatus can be made to be compact.

“Magnetic member” is made of for example, para-magnetic materials orsuper para-magnetic materials.

A fourth aspect of the invention is an apparatus for an integratedprocess of magnetic particles according to the second or the thirdaspect of the invention, wherein the nozzle outer member or a part ofthe nozzle comprises divided parts that are divided in two, wherein thedivided parts are apart from one another in a manner that the dividedparts have mutually opposite magnetic polarities.

The distance between the divided parts is one which can give anappropriate magnetic force within the nozzle. The distance is determinedby considering the strength of the magnetic field of the magneticsource, the kinds of magnetic materials, the size of the throughsection, each location of the through section, or the distance from themagnetic source, the size of the magnetic force device, and the magneticforce necessary for the processes etc. When the distance between thedivided parts is the shortest in the magnetic force device, the maximummagnetic force can be generated there compared to the sections having alonger distance between the divided parts.

With the present invention, the divided parts are apart from each otherso that the lines of magnetic force can leak out in the places whererequired, and an appropriate magnetic force can be efficiently appliedto the nozzle, without wastage, by leakage of the lines of magneticforce.

A fifth aspect of the invention is an apparatus according to the fourthaspect of the invention, wherein the magnetic force device comprises amagnetic source having an electromagnet or a permanent magnet, twomagnetic plates made of magnetic material and connecting with theelectromagnet or capable of connecting with the permanent magnet andcapable of being magnetized and demagnetized, and mounted inface-to-face relationship in a low and a high position, plural throughsections penetrating the two magnetic plates and capable of takinginsertion of the nozzles, a pair of projections mounted in each throughsection, projecting to the opposite surface of each magnetic plate andmade of magnetic materials, wherein the pair of the projectionscorrespond to the nozzle outer member, and each projection correspondsto the divided parts and are apart from one another in such a mannerthat they have mutually opposite polarities by magnetization.

When an electromagnet is used as the magnetic source, generation andextinguishment of magnetic fields are executed by conducting and cuttingoff the electric currents, respectively. When a permanent magnet is usedas the magnetic source, the magnetization and demagnetization can beexecuted by mounting and dismounting or touching and detaching. Touchingand detaching are executed by for example, rotating a permanent magnetabout an axis of rotation and touching or approaching, or separating thepole thereof to or from the magnetic member respectively.

“The magnetization and demagnetization” can be executed at positions farfrom each nozzle, without providing a driving mechanism or a drive spacefor each nozzle, by mounting and dismounting the permanent magnet to andfrom magnetic plates magnetically connecting with the wall parts mountednear each nozzle and made of magnetic material, or by conducting andcutting off the electric current. It thus follows that a plurality ofnozzles can be arranged in an integrated state.

With the present invention, since the magnetic field being generatedbetween the projections can be stronger than that, generated between themagnetic plates, the strong magnetic field leaking out between theprojections can be applied to the nozzles, by mounting the projectionsprojecting toward the opposite surfaces of the magnetic plates at apredetermined interval. “A predetermined interval” is the distance thatdoes not affect magnetic fields irrelevant to the process and thatallows the nozzle to penetrate the through section.

A sixth aspect of the invention is an apparatus according to the fifthaspect, wherein the through section comprises through holes penetratingthrough the magnetic plates and projecting vertically and capable oftaking insertion therethrough by the nozzles, and each wall part of themutually separated through holes has opposite polarity respectively.

With the present invention, the magnetic field can be efficientlyapplied to within the nozzle without waste.

A seventh aspect of the invention is an apparatus according to the fifthaspect, wherein the magnetic force device comprises one or more magneticsources, the magnetic source comprises a coil and a magnetic elementprovided with the coil, and one end of the magnetic element is connectedwith one of the two magnetic plates and the other end thereof isconnected with the other thereof.

With the invention, since each magnetic plate connects with only one endor the other end of the magnetic element serving as the magnetic source,the magnetic plates are not directly touched. Therefore, a strongermagnetic field can be generated between the divided parts whose distanceis shorter than that between the magnetic plates.

An eighth aspect of the invention is an apparatus according to theseventh aspect, wherein the magnetic elements are mounted outside of thespace which is formed by the magnetic plates.

With the invention, since the magnetic elements are mounted outside ofthe space sandwiched between the magnetic plates, the turn number of thecoil is not restricted by the interval between the magnetic plates, anda strong magnetic force can be generated.

A ninth aspect of the invention is an apparatus according to the eightaspect, wherein the magnetic elements comprise a first part and a secondpart which are separately mounted, wherein one end of the first partconnects with one of the two magnetic plates, the other end of thesecond part connects with the other magnetic plate, wherein the firstpart and the second part are overlapped and are wound by wire of a coil,or the other end of the first part and one part of the second part areconnected with each end of the third part and wound by wire of the coiland made of magnetic material.

With the invention, the magnetic element and magnetic plate can beeasily produced by separating the magnetic element into a few simplyformed parts.

A tenth aspect of the invention is an apparatus according to the fourthaspect, wherein divided parts being apart from one another, are taperedtoward a gap. With the invention, since the line of the magnetic fieldcan be densely generated on the outer side of the nozzle near the gap, astrong magnetic field can be applied to the nozzle. The tapered formimplies for example, a truncated cone.

An eleventh aspect of the invention, is an apparatus according to thefifth aspect, wherein the pair of projections project from the openingedge of the through section of one of the magnetic plates to the othermagnetic plate in a direction of insertion of the nozzle opposite to oneanother, and each tip of the projections is apart from the oppositesurface at a first interval, and the tips of the projections are apartfrom one another separated from the nozzle at a second interval shorterthan the first interval, in such a manner that the tips have oppositepolarities, respectively.

The reason that the second interval is formed so as to be shorter thanthe first interval is so that the lines of the magnetic force candensely pass between the projections which are apart at the secondinterval.

A twelfth aspect of the invention is an apparatus according to the thirdaspect, wherein each through section of the magnetic force devicecomprises a separate hole in which the nozzle is inserted in a way thatthe outer surface of the nozzle can come in contact with or approach tothe nozzle outer member, and an insert-withdraw hole mounted adjacent tothe separate hole and having an opening larger than that of the separatehole so that the nozzle can horizontally move to and from the separatehole and can be withdrawn and inserted at the insert-withdraw hole.

The present invention needs a moving mechanism which can horizontallymove the nozzle between the separate hole and the insert-withdraw holeand can vertically move the nozzle at the insert-withdraw hole, relativeto the magnetic force device, as a precondition. The reason why theinsert-withdraw hole is provided in addition to the separate hole is asfollows.

A liquid is necessarily stuck on the periphery of the lower part of thenozzle which touches with the liquid accommodated in the vessel. Sincethe nozzle outer member mounted in the separate hole approaches ortouches the nozzle, the liquid stuck to the periphery of the lower partmay stick to the nozzle outer member and stain the nozzle outer memberin the case where the nozzle comprising a pipette tip is pulled up fromthe through section. Once that happens, the nozzle outer member isstained, the nozzle outer member stains newly inserted nozzles, andcross-contamination may occur. Therefore, the nozzle is inserted in orwithdrawn out from the through section, through the insert-withdraw holewhose opening is larger than that of the separate hole, so that thenozzle does not touch other members.

A thirteenth aspect of the invention is an apparatus according to thetwelfth aspect, wherein the nozzle comprises a small diameter sectionand a larger diameter section, the separate hole has an opening thatonly the small diameter section can be inserted in, and theinsert-withdraw hole has an opening that the larger diameter section canbe inserted in.

With the invention, in the case where the nozzle has a small diametersection and a larger diameter section, the insert-withdraw hole has anopening that can take insertion of the larger diameter section. Thus,the opening can take insertion of the larger diameter section.Consequently the insert-withdraw hole is not stained by the smalldiameter section which is mounted in the lower section and touches theliquid, and cross contamination can be prevented. Further, since eventhe larger diameter section can be withdrawn and inserted, the nozzlecan be easily inserted and withdrawn.

A fourteenth aspect of the invention is an apparatus according to thefirst aspect, wherein the magnetic force device can apply and remove themagnetic force to and from the nozzle with remaining stationary neareach nozzle exterior.

With the invention, a uniform strong magnetic field can be applied toeach nozzle at point-blank range.

Besides, the coil of the magnetic force device may be made of a singlewire. Therefore, since ports etc. need not be Mounted per coil, thestructure of the circuits can be simplified. Furthermore, since the coilis not mounted on the nozzle, the nozzle can be disposed of.

A fifteenth aspect of the invention is an apparatus according to thefirst aspect, wherein the magnetic force device comprises an insulatingdevice for preventing heat generated by magnetization or generation of amagnetic field, from being transmitted toward the nozzle. With theinvention, detrimental influence of heat on the nozzles can be avoided.Conversely, in a special case the heat may be positively utilized forthe process without the insulating device. The insulating device may beone included in the fifteenth aspect, one provided by a Peltier effectelement, or one provided for insulation against the magnetic sources.

A sixteenth aspect of the invention is an apparatus according to thefifteenth aspect, comprising a ventilator for sending air to themagnetic force device or the neighborhood thereof. Thus, transmission ofheat to the nozzle can be efficiently prevented.

A seventeenth aspect is an apparatus according to the second aspect,wherein the magnetic force device comprises plural magnetic sources, andplural segments defined so as to include the area spatially near eachmagnetic source, respectively. For example, belt-like magnetic segmentshaving through sections capable of taking insertion of a column ofnozzles selected from the nozzles arranged in a plane-like state, arearranged in the direction of the magnetic field and have the same numberof rows as the nozzles.

Therefore, in the case of manufacturing such a magnetic force devicethat can process a fluid by using a vessel having a plurality of liquidcontaining parts, the magnetic force device can be manufactured by beingdivided and the production cost can be reduced. The magnetic field canbe uniformly distributed and a strong magnetic field can be applied.

An eighteenth aspect of the invention is an apparatus according to thethird aspect, wherein the magnetic force device comprises a magneticsource having a permanent magnet or an electromagnet, and a plank-likemember made of magnetic material and magnetically connected to theelectromagnet or capable of magnetically connecting to the permanentmagnet, wherein the through sections are provided in the plank-likemember and are capable of taking insertion of the nozzles. With theinvention, a magnetic force device having a simple structure isprovided. For instance, “the plank-like member” may be formed by pilingup thin plates made of magnetic material in the direction of magneticforce. With the invention, since the lines of magnetic force can begenerated in the direction of the surfaces of the thin plates, leakageof magnetization can be suppressed to the minimum, and a uniformmagnetic field can be obtained. Further, the thin plates can be piled upin a stratified state so that the normal direction of the thin plates isvertical or horizontal.

A nineteenth aspect of the invention is an apparatus according to theeighteenth aspect, wherein the through holes of the magnetic forcedevice comprise divided wall parts divided in the direction of theinsertion of the nozzle in such a manner that divided wall parts areapart from one another and have opposite polarities by magnetization.

A twentieth aspect of the invention is an apparatus according to thenineteenth aspect, wherein the nozzles comprise a larger diametersection and a small diameter section, and the plank-like member of themagnetic force device comprises plural column-like members arrangedapart from each other at intervals capable of taking insertion of thelarger diameter section of the nozzle, and plural protrusions made ofmagnetic material that are projected oppositely from each column-likemember, magnetized in a manner that has opposite polarity to each otherand arranged apart from each other at intervals capable of takinginsertion of the smaller diameter section of the nozzle, and arearranged along the column-like member at intervals capable of takinginsertion of the larger diameter section of the nozzle, wherein oppositepointed ends of the protrusions correspond with the divided wall parts.With the invention, since each column-like member is apart from eachother, the lines of magnetic force run through the narrow intervalbetween the pointed ends of the opposite protrusions. Therefore, astrong magnetic force can be supplied to the nozzles.

A twenty first aspect of the invention is an apparatus according to thesecond aspect, wherein the magnetic force device comprises a plank-likemember made of magnetic material, plural through holes capable ofpassing a fluid and mounted in the plank-like member, small diameterpipes communicating with the through holes and capable of being insertedinto a vessel and mounted under the through holes, wherein the throughholes and the small diameter pipes serve as the nozzles. With theinvention, since the nozzle itself constitutes the magnetic forcedevice, the number of the members can be reduced, the apparatus can beformed to be compact, and a strong magnetic field can be applied intothe nozzles.

A twenty second aspect of the invention is an apparatus according to thefirst aspect, wherein the drawing/discharging device comprises areservoir body comprising plural reservoirs for storing a drawn fluidand communicating with the nozzles, and an increasing/decreasing devicefor increasing and decreasing pressure within the reservoirs and thenozzles in a manner that draws or discharges the fluid. The “reservoirs”can store a fluid. It follows that the reservoirs can store not only aliquid, but also a gas such as air. Thus, a process can be executed in astate that an air layer can be formed between the drawn or dischargingliquid and the increasing/decreasing device or, a cleaning liquid. Theshape of the reservoirs may be for example, hole-like with a bottom,with no bottom, with a lid, or with no lid, or pipe-like, orvessel-like. Further, the reservoirs may be integrated with the nozzlesor be separate from the nozzle. Furthermore, the number of reservoirsneed not be the same to that of the nozzles.

For example, plural nozzles may communicate with a single reservoir. Inthe case where the number of nozzles is the same to that of thereservoirs, each nozzle may communicate with each reservoir one to one.Further a part of plural nozzles may jointly communicate with a singlereservoir, or plural reservoirs may jointly communicate with a singlenozzle.

Furthermore, the reservoir body which is an assembly of reservoirs, maybe not only a plank-like one provided with plural hole-like reservoirs,but may be one with plural pipe-like or vessel-like reservoirs,assembled in a bundle.

With the invention, plural reservoirs can be simply manufactured in anintegrated state by for example, piercing plural pits in the plank.

Moreover, the pressure may be increased and decreased by raising andlowering a sliding body as described in the fifteenth aspect. Further,the reservoir may have an expandable bellow mounted in a part of theside thereof and an opening connecting to the nozzle in a lower sidethereof. The increasing/decreasing device may be a pressing device whichpresses the reservoirs and release the pressing of the reservoirs.

Furthermore, the increasing/decreasing device may comprise an insertingbody which is made of an elastic solid at least partially, which can beinserted into the reservoirs by deformation and cover the top of thereservoirs, and a pressing device for pressing the inserting body forcompressing the inside of the reservoir and releasing pressing thereof.Further, the reservoir may have a diaphragm and an opening mounted inthe lower side thereof for connecting with the nozzle, and theincreasing/decreasing device may be a pressing device for pressing thediaphragm and releasing pressing thereof.

A twenty-third aspect of the invention is an apparatus according to thetwenty-second aspect, wherein the increasing/decreasing device comprisesa sliding body capable of moving vertically to and from the reservoirbody, and sliding projections projecting downward from the sliding bodyand capable of sliding through the nozzle in such a manner that thepressure within the reservoirs or nozzles increases or decreases.

With the invention, the apparatus has a simple construction. A fluid canbe easily drawn or discharged with the same conditions for time,capacity and timing etc., all together, by moving the sliding bodyhaving plural sliding projections, to and from the reservoir bodyvertically.

A twenty-fourth aspect of the invention is an apparatus according to thetwenty-third aspect, wherein the sliding projections are formed to havea two-step structure comprising a larger diameter section capable ofsliding through the reservoir formed to be pit-like, and a smallerdiameter section capable of extending along the axes of the largerdiameter section and sliding through the nozzle communicating with thereservoir.

With the invention, when a relatively large amount of fluid is handled,drawing or discharging is executed by moving the sliding projectionsvertically in a state with the tip of the small diameter section and thetip of the larger diameter section fixed and aligned. On the other hand,when a relatively minute amount of fluid is handled, first, the slidingprojections are moved vertically in a state with the tips of the smalldiameter section and the larger diameter section fixed and aligned. Whenthe tips of the sliding projections stick to the lower part of thereservoir, drawing or discharging is executed by sliding only the smalldiameter section through the nozzle, vertically.

Thus, minute amounts of fluid as well as a relatively large amount offluid can be processed at high precision. Therefore, an apparatus withreliability and diversity can be provided.

With the invention, residual liquid or remnants such as magneticsubstances or particles remaining in the nozzles can be surely andefficiently discharged. Therefore the process for a fluid can bereliably executed.

Further, since the nozzles can be recycled by completely cleaning thenozzle with a cleaning liquid, cost for the process can be reduced incomparison to the case of using disposable nozzles or reservoirs. Here,though the sliding projection is formed to be two-steps, if necessary,the sliding projection may be formed to be multi-steps.

A twenty-fifth aspect of the invention is an apparatus according to thetwenty-second aspect, wherein the nozzles comprise a tip capable ofbeing mounted to and dismounted from the drawing/discharging device.

With the invention, cross contamination can be surely avoided withoutcleaning the nozzle. Therefore, since drawing and discharging can beexecuted through an air layer formed within the reservoir, the processcan be efficiently executed, without cleaning.

A twenty-sixth aspect of the invention is an apparatus according to thetwenty-fifth aspect, comprising a pushing body having pushing pipesinserted from the upper side of the reservoirs into the reservoirs andcapable of pushing the nozzles out of the reservoirs, wherein thenozzles are detachably mounted to the reservoirs while being insertedfrom the lower side of the reservoirs, and the increasing/decreasingdevice comprises a sliding body having plural sliding projectionsprojecting downward, capable of sliding through the pushing pipe andcapable of moving vertically to and from the reservoirs respectively, ina manner that the pressure within the reservoirs or nozzles can beincreased or decreased.

With the invention, since the process can be executed in such a mannerthat drawing or discharging liquid is apart from the pushing body by anair layer, cross contamination can be surely prevented by exchangingonly the nozzle. Furthermore, the nozzles are detachably mounted to thereservoirs, and the nozzles can be easily dismounted all together bymoving the pushing body downward.

A twenty-seventh aspect is an apparatus according to the twenty-fifthaspect, wherein the nozzles are detachably mounted to the lower part ofpit-like reservoirs and are inserted to a predetermined depth in thepit-like reservoirs, the sliding projections can slide to a depth of theinstallation depth of the nozzles in the reservoirs, and a projectinglip part is projected from the outer side of the nozzles exposed underthe magnetic force device for mounting and dismounting, and astroke-down plate provided with plural small hole parts with respectivediameters larger than that of the nozzles and smaller than that of thelip parts is mounted between the magnetic force device and , the lipparts in a way that the hole parts take insertion of the nozzles and thenozzles can be detached by moving the stroke-down plate down.

With the invention, the nozzle can be easily detached by moving thestroke-down plate downwards. Further, the sliding, projections do nottouch with the liquid, and cross contamination can be surely preventedwhile drawing and discharging the liquid etc. through the medium of theair layer within the reservoir.

A twenty-eighth aspect is an apparatus according to the twenty-thirdaspect, wherein an inner wall of the upper part of the reservoir isformed to be cylindrical, and that of the lower part of the reservoir isformed to be funnel-shaped and is connected with the nozzles. With theinvention, since the lower part thereof is formed to be funnel-shapedand the tip of the sliding projections is formed so as to fit closelywith the lower part of the reservoir, residual liquid can be surelyavoided and a process can be reliably executed.

A twenty-ninth aspect of the invention is an apparatus according to thefirst aspect, wherein the magnetic force device is constructed to beable to relatively move to and from the drawing/discharging device orthe nozzle. With the invention, since the magnetic force device isconstructed as mentioned above, the magnetic force device can surelyapply and remove the magnetic force. For example, after the magneticforce by the magnetic force device is removed, the process fordischarging etc. is executed by moving the drawing/discharging deviceupwards and keeping the nozzle away from the magnetic force device sothat the effect by residual magnetization can be reduced. Furthermore,in the case where the nozzle is detachably mounted to thedrawing/discharging device, the nozzle can be easily detached.

A thirtieth aspect of the invention is an apparatus according to thetwenty second aspect wherein a cleaning liquid can be poured into eachreservoir from the top or side of the reservoir body.

The invention is embodied, for example, by connecting the reservoir tothe vessel accommodating the cleaning liquid by mounting a change-overvalve at some midpoint of a hose connecting between the reservoir bodyand the increasing/decreasing device, or by providing a passagecommunicating with the vessel accommodating the cleaning liquid, in theside wall of the reservoir body. Further, it may be embodied bydetaching the sliding projections and inserting a cleaning liquid pipe,instead of the detached sliding projections, or by providing a pipe forpouring a cleaning liquid into the sliding projection per se and so on.With the invention, since the vessel accommodating the cleaning liquidneed not be transported, the process can be efficiently executed.

A thirty first aspect of the invention is an apparatus according to thefirst aspect, comprising a light measuring device for receiving lightfrom all the vessels or plural liquid containing parts simultaneously orall together and measuring the strength of the light or processing thelight as an image in order to measure a state of light emission.

With the invention, measuring light emission can be easily, efficientlyand reliably executed, in comparison to the case where measurement ofliquid emission is executed by moving a PMT device per liquid containingpart or by mounting a PMT device for each liquid containing part.

A thirty second aspect of the invention is an apparatus according to thethirty first aspect, wherein the light measuring device comprises pluralreceiving components mounted at places corresponding to the liquidcontaining parts and having the same number as that of the liquidcontaining parts, and shading fences mounted between neighboringreceiving components for preventing light from entering to other thanthe corresponding liquid containing part.

A thirty third aspect of the invention is a magnetic apparatuscomprising, plural outer members capable of being mounted to anddismounted from a pipette device having a drawing/discharging device fordrawing and discharging a liquid, and plural nozzles through theinterior of which liquid passes due to the drawing and discharging, oneor more vessels arranged with plural liquid containing parts, or columnclusters arranged by plural columns, and capable of being brought intocontact with or approaching to each outer surface of each nozzle, eachliquid containing part or each column, while being mounted to thepipette device, the vessel or the column cluster, and a magnetic forcedevice for applying a magnetic force to or removing the magnetic forcefrom each nozzle, each liquid containing part or each column in a statewith remaining stationary, by magnetizing and demagnetizing the outermembers or by generating or extinguishing the magnetic field with coilswhich are mounted around each nozzle, each liquid containing part oreach column while fitting to the pipette device, the vessel or thecolumn cluster.

“Column” means a liquid containing part comprising at least a mechanismcapable of discharging a liquid such as a valve, and another mechanismfor selectively drawing a liquid such as a valve.

With the invention, since the magnetic device can be mounted onto apipette device, a vessel or a column cluster, and the process for targetsubstances combined with the magnetic particles can be accumulated byutilizing the already existing pipette device, vessel or column cluster,and be utilized, the process can be executed at low cost.

A thirty fourth aspect of the invention is a magnetic apparatusaccording to the thirty third aspect, wherein the magnetic force deviceis the magnetic force device according to any one of the third to twentyfirst aspects applied to the nozzles, liquid containing parts orcolumns.

With the invention, the magnetic apparatus is applied to not only thepipette device arranged with plural nozzles but also to a vesselarranged with plural liquid containing parts or a column clusterarranged with plural columns. In the latter two cases, since themagnetic force device is applied to the liquid containing parts orcolumns, the diameter of each through section etc. is changed accordingto the liquid containing part or column.

A thirty fifth aspect of the invention, is an apparatus according to anyone of the first to the thirty fourth aspects, wherein plural nozzles,plural through sections, plural reservoirs, plural sliding projections,plural hole parts, plural pushing pipes, plural liquid containing partsof the vessel, plural columns of the column cluster or plural receivingcomponents are arranged in a plane-like state with a predeterminedperiodicity or a predetermined symmetry such as plural row-shaped,matrix-shaped, annular ring-shaped, polygonally, or radially.

“Matrix-shaped” means a state where plural elements are arranged atleast in two directions (row direction and column direction) or inparallel, in a plane-like state. “Row” means the arrangement in the rowdirection, while “column” means the arrangement in the column direction.The row direction and the column direction need not always cross at 90°.These directions may cross obliquely. Further, these plural elements maybe arranged in a dense state while being alternately shifted by onebetween the neighboring rows or columns.

With the invention, integration can be facilitated. Since pluralelements are arranged with a predetermined periodicity or symmetry,rotating movement and transposed movement (rows and columns areexchanged one with another) are possible by the pipette device accordingto the symmetry, and the control of movement and standardization arefacilitated.

A thirty sixth aspect of the invention, is an apparatus comprising areservoir body provided with plural pit-like reservoirs for storingdrawn liquid arranged in a matrix, a sliding body with jutting pluralsliding projections sliding through the reservoirs and capable of movingvertically to and from the reservoir body, plural nozzles attached tothe lower parts of the reservoirs and capable of passing the liquidtherethrough, a magnetic force device capable of magnetization anddemagnetization having plural through sections in which is inserted eachnozzle and having a wall part in contact with or near the outer sidesurface of the nozzle, with the nozzles inserted thereinto, wherein eachwall part has two divided wall parts being apart from one another insuch a manner that the divided wall parts have opposite polarities bymagnetization, respectively.

A thirty seventh aspect of the invention is an apparatus according toany one of the first to thirty second aspects, the thirty fifth aspect,and the thirty sixth aspect, comprising a driving mechanism for drivingthe drawing/discharging device to draw and discharge, a magneticcontroller for controlling the magnetic force of the magnetic forcedevice, a transfer mechanism for transferring between vessels placedoutside the pipette device, and the drawing/discharging device and themagnetic force device or between the drawing/discharging device and thenozzles and the magnetic force device, and an integrated processcontroller for controlling an integrated process of magnetic particlesby controlling at least the driving mechanism, the magnetic controller,and the transferring mechanism according to instructions.

“Transferring” implies horizontal transferring, vertical transferring orrotational transferring. “Rotational transferring” includes transferringby transposition.

With the invention, since the driving mechanism, the magnetic controllerand the transferring mechanism can be handled by a single controller ina coordinated fashion, efficient, diverse and reliable control can beexecuted.

A thirty eighth aspect of the invention is an apparatus according to thethirty seventh aspect, wherein the controller controls an insulatingdevice such as a ventilator, the pouring of cleaning liquid, a lightmeasuring device, and data analysis, data disposition, or data output.

A thirty ninth aspect of the invention is an apparatus according to thethirty seventh aspect, wherein the controller controls either thestrength, direction, or application time of the magnetic force, ormagnetic patterns obtained from various combinations of strength,direction and time, according to the contents, conditions or objects ofa target controlling step, the fluid, substances such as reagents,kinds, shape, quantity, combining state, or size of the magneticparticles, the pressure, the fluid velocity, the number of times ofdrawing/discharging, processes of transferring, agitation, cleaning,separation, removal extraction, reaction, clarification, concentration,dilution, recovery, isolation, or resuspension, external surroundingssuch as temperature, structure of the apparatus, materials or size ofthe apparatus, progress or schedule of magnetic control, degree of theresidual magnetization, or instructions from the outside.

The degree of residual magnetization is obtained by measuring themagnetization with a coil of the magnetic force detecting device mountednear the apparatus or nozzle thereof. The measured results are fed backto the magnetic force device for use in control of the magnetic forcedevice.

With the invention, according to the contents of the steps etc.,precise, efficient, and reliable processes can be executed bycontrolling delicately to vary the strength, direction, or time forapplying the magnetic field or the magnetic pattern obtained from acombination of the strength, direction, or time.

A fortieth aspect of the invention is an apparatus according to thethirty ninth aspect, wherein the controller controls in such a mannerthat the direction of the magnetization controlled by the magneticcontroller is alternately reversed each time the magnetization is pausedby demagnetization.

Therefore, since the direction of the magnetization in the wall partsetc. of the magnetic force device is alternately reversed, residualmagnetization is offset, and magnetic noise due to the residualmagnetization is reduced, even if the wall part is made of a para-magnetsuch as iron.

A forty first aspect of the invention is an apparatus according to thethirty ninth aspect, wherein the magnetic controller controls in such amanner that the direction of the magnetization is reversed with astrength or a driving time corresponding to that of the non-reversedmagnetization, when changing a magnetized state to a demagnetized state.

Thus, generation of residual magnetization is prevented or the affect ofthe residual magnetization is reduced by generating magnetization thatcan offset the residual magnetization generated by the magnetization,according to the extent of the magnetization immediately beforedemagnetization.

A forty second aspect of the invention is a method comprising the stepsof: drawing or discharging all together a fluid to or from a vesselcomprising plural liquid containing parts by a drawing/dischargingdevice mounted in the apparatus for an integrated process according toany one of the first to thirty second aspects, or the thirty fifth toforty first aspects, and applying the magnetic force to or removing themagnetic force from the nozzles in a state that remains stationary nearthe nozzles exterior, by generating or extinguishing the magnetic fieldwith magnetization and demagnetization of the nozzle outer membersmounted in contact with or near the periphery of the nozzles or a partof the nozzles, or by generation or extinguishing the magnetic fieldwith a coil wound around the periphery of each nozzle.

A forty third aspect of the invention is a method according to the fortysecond aspect comprising further the steps of: mixing magnetic particlesand the target substances by drawing and discharging all together withthe apparatus for an integrated process, to make a suspensionincorporating the magnetic particles combined with the target substancesin plural liquid containing parts of the vessel, processing forseparation by adhesion to the inner walls of the nozzles, eliminationfrom the inner walls, transferring, resuspension, agitation,dissociation, extraction, reaction, clarification, concentration,dilution, recovery, isolation, or cleaning of the magnetic particlescombined with the target substances by applying the magnetic force to,or removing a predetermined magnetic force from magnetic particlescombined with the target substances within the nozzles, while drawingand discharging the liquid.

“Dissociation” means removal of magnetic particles from the targetsubstance, and “extraction” means the removal of the magnetic particlescombined with the target substance, or only the target substance.

A forty forth aspect of the invention is a method according to the fortysecond aspect or the forty third aspect, further comprising a step formeasuring all together light emission of the liquid accommodated in eachliquid containing part and processed by the apparatus for an integratedprocess.

A forty fifth aspect of the invention is a method according to the fortythird aspect, wherein the apparatus for an integrated process formagnetic particles whose plural nozzles are arranged in a matrix isused, and the processing for the transferring step comprises atransposed moving step for moving in such a manner that rows and columnsof the nozzles of the apparatus for an integrated process or the liquidcontaining parts of the vessel, are exchanged, or a horizontal movingstep for transferring in such a manner that rows and columns are notexchanged.

With the invention, combinations of a variety of substances can beefficiently and reliably generated all together by the transposed movingand the horizontal moving or a repetition of these movements.

A forty sixth aspect of the invention is a method of making any combinedsubstances in carriers by arbitrarily combining with plural elements ofsubstances, comprising the steps of: dispensing peach liquidincorporating each element of substances into one or more groups ofcontaining parts arranged by plural containing parts in a matrix inwhich the containing parts accommodating said carriers are arranged inrows or columns having a predetermined number width in a way so as to beincluded in the matrix, according to the structure of the specifiedcombined substances or the utilized kinds of containing parts, andmixing the dispensed elements of substances into the group of thecontaining parts accommodating the carriers, with the elements ofsubstances arranged in rows or columns having a predetermined numberwidth, in such a manner that row-like or column-like arrangements of thedispensed elements of substances are positioned against row-like orcolumn-like arrangements of the elements of substances in a state oftransposition or non-transposition.

“Element of substances” implies for example, genetic substances such asDNA or RNA etc., or amino acids, “combined substances” implies forexample, a variety of compounds such as DNA, RNA or peptides etc.

The invention may apply to not only the process using the magneticparticles as carriers, but also the process using the non-magneticparticles as polymer carriers. The vessel may have the liquid containingparts arranged in a matrix and may have a capturing function by mountingfor example, a filter. Instead of vessels, columns arranged in a matrixand having a capturing function, may be used. The carriers may be solidcarriers which are fixed to the surface of the liquid containing partsarranged in a matrix. Further, instead of having a capturing function inthe vessel, a pipette device for drawing and discharging liquid, mayhave a capturing function by mounting a magnetic force device.

With the invention, combined substances of various structures can beintegratedly generated by mixing the liquid incorporating elements ofsubstances in such a manner that the row-like or column-likearrangements of liquids are transposed or non-transposed in a matrix.The invention may apply to combinatorial synthesis. The function forcapturing the magnetic particles is embodied by the magnetic forcedevice according to the thirty-third or the thirty-forth aspect.

A forty-seventh aspect of the invention, is a method according to theforty-sixth aspect for when the containing parts are liquid containingparts provided in a vessel and arranged in a matrix, comprising thesteps of: disposing the carriers in the liquid containing parts of oneof the one or more vessels, dispensing each liquid incorporating eachelement of substances into one or more vessels including vessels inwhich the carriers are disposed, in a state with rows or columns havinga predetermined number width, according to the structure of the combinedsubstances, and mixing each liquid incorporating each element ofsubstances and disposed in a state with rows or columns having apredetermined number width in the other one or more vessels, with thedispensed liquid incorporating the elements of substances into thevessels in which the carriers are disposed, in such a manner thatrow-like or column-like arrangements of the dispensed elements ofsubstances are positioned against row-like or column-like arrangementsof the elements of substances in a state of transposition ornon-transposition.

The invention may apply to the case where the magnetic particles areused as carriers (in the case including the case where a capturingcarrier function is provided for the vessels, or a capturing carrierfunction is provided for the pipette device), the carriers are solidcarriers fixed in the liquid containing parts, or the carriers arenon-magnetic particles and the carrier capturing member is mounted inthe vessels. The capture of the magnetic particles can be executed bythe magnetic force device according to the thirty-third or thethirty-forth aspect.

A forty-eighth aspect of the invention is a method according to theforty-sixth aspect, for when the containing parts are plural columnsarranged in a matrix and having a function for capturing carrierscomprising the steps of, disposing the carriers to each column having acapturing function, dispensing each liquid incorporating each element ofsubstances into the columns arranged in a matrix in a state with rows orcolumns having a predetermined number width, according to the structureof the specified combining substances, mixing the dispensed elements ofsubstances into the group of the group of the columns accommodating thecarriers, with the elements of substances arranged in rows or columnshaving a predetermined number width, in such a manner that row-like orcolumn-like arrangements of the dispensed elements of substances arepositioned against the row-like or column-like arrangements of theelements of substances in a state of transposition or non-transposition.

The invention may apply to the case where the carriers are magneticparticles or non-magnetic particles, or solid carriers. In the casewhere the carriers are magnetic particles, the capturing carrierfunction may be embodied by a magnetic field. In the case where thecarriers are non-magnetic particles, the capturing carrier function maybe embodied by a filter. In the case of solid carriers, the solid phaseper se has the capturing function. The capturing magnetic particlesfunction may be embodied by the magnetic force device according to thethirty-third aspect or the thirty-forth aspect.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a separated perspective view showing an apparatus for anintegrated process according to a first embodiment of the presentinvention.

FIG. 2 is a view showing a magnetic force device according to a firstembodiment of the present invention.

FIG. 3 is a cross-sectional view taken on line A—A in FIG. 1, showing anapparatus for an integrated process according to a first embodiment ofthe present invention.

FIG. 4 is a cross-sectional view showing an assembled apparatus for anintegrated process according to a first embodiment of the presentinvention.

FIG. 5 is an exploded perspective view of an apparatus for an integratedprocess according to a second embodiment of the present invention.

FIG. 6 is a cross-sectional assembled view taken on line B—B in FIG. 5,showing an apparatus for an integrated process according to the secondembodiment of the present invention.

FIG. 7 is a cross-sectional view showing an apparatus for an integratedprocess according to a third embodiment of the present invention.

FIG. 8 is a cross-sectional view showing an apparatus for an integratedprocess according to a fourth embodiment of the present invention.

FIG. 9 is a cross-sectional view showing an apparatus for an integratedprocess according to a fifth embodiment of the present invention.

FIG. 10 is a cross-sectional view showing an apparatus for an integratedprocess according to a sixth embodiment of the present invention.

FIG. 11 is a perspective view showing a nozzle according to the sixthembodiment of the present invention.

FIG. 12 is a view showing a concept for a process according to a seventhembodiment of the present invention.

FIG. 13 is a view showing a magnetic force device according to any oneof eighth to twelfth embodiments of the present invention.

FIG. 14 is a view showing a magnetic force device according to athirteenth embodiment of the present invention.

FIG. 15 is a view showing a magnetic force device according to afourteenth embodiment of the present invention.

FIG. 16 is a view showing another magnetic force device according to thefourteenth embodiment of the present invention.

FIG. 17 is a view showing another magnetic force device according to afifteenth embodiment of the present invention.

FIG. 18 is a view showing a magnetic force device according to asixteenth embodiment of the present invention.

FIG. 19 is a view showing a magnetic force device according to aseventeenth embodiment of the present invention.

FIG. 20 is a view showing an apparatus for an integrated processaccording to an eighteenth embodiment of the present invention.

FIG. 21 is a plane view showing an apparatus according to a first priorart.

FIG. 22 is a perspective view showing an apparatus according to a secondprior art.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS FIRST EMBODIMENT

An apparatus for an integrated process for magnetic particles (referredto hereunder as “an apparatus”) according to a first embodiment of thepresent invention is described on the basis of FIGS. 1 to 4.

As shown in FIG. 1, the apparatus 10 comprises a plank-like reservoirbody 12 where plural (96 in this example) cylinders 11 (11 _(1,1)˜11_(12,8)) serving as pit-like reservoirs are pierced and arranged, in aplane state (in a matrix having 12 rows×8 columns in this example).

Plural nozzles 13 communicating with each cylinder 11 are mounted underthe reservoir body 12, and formed integral with the reservoir body 12,in a way that the nozzles project downwards from the reservoir body 12.The length and the diameter of the nozzles 13 are determined so that theplural nozzles 13 can be inserted into plural hole-like liquidcontaining parts (holes) 15 (15 _(1,1)˜15 _(12,8)) provided in a vessel14 placed under and outside the apparatus 10, and having a capacitylarge enough to store the liquid of the liquid containing parts 15.

Further a moving mechanism (not shown) is mounted in such a manner thateither or both of the reservoir body 12 and a stage on which the vessel14 is placed can move vertically, horizontally and rotatatively relativeto each other. For example, a link mechanism, a cam mechanism, a ballscrew mechanism, a stepping motor or a DC motor is utilized as the abovemoving mechanism.

A magnetic force device 16 capable of applying and removing a magneticforce to and from within each nozzle 13 respectively in such a mannerthat the neighborhood of the outside of each nozzle 13 remainsstationary, is mounted under the reservoir body 12 and above the vessels14.

The magnetic force device 16 comprises an upper plate 18 a and a lowerplate 18 b which are made of magnetic material and are mountedoppositely at a predetermined interval, and are capable of beingmagnetized and demagnetized.

The two plates 18 a, 18 b are supported and fixed by support pillars 18c which are sandwiched by edges 18 d thereof. A coil 19 is mounted insuch a manner that a conductive wire is wound around the side of thesupport pillar 18 c. The coil 19 connects with a switch and power sourcewhich are not shown in the drawings, and constitutes an electromagnetcapable of generating and extinguishing the magnetic field. It ispreferable to form steps between the edges 18 d and the upper plate 18 aso that the turn number of the coil 19 can be larger.

On the surfaces of the upper plate 18 a and the lower plate 18 b whichface one another, plural projections 17 a, 17 b made of magneticmaterial are formed to be tapered off in a substantially truncated coneand are mounted separately or as one piece to each plate 18 a, 18 b insuch a manner that they project at the locations corresponding to thenozzles, and are arranged in a matrix.

The tips of the projections 17 a, 17 b are mounted so as to be apartfrom one another without contact.

At the projections 17 a, 17 b, through sections 17 capable of takinginsertion of the nozzles 13 respectively, are mounted in such a mannerthat they penetrate the upper plate 18 a, the lower plate 18 b and theprojections 17 a, 17 b vertically. Each wall part of the throughsections 117 is capable of being magnetized and demagnetized, and is incontact with or near the upper part or intermediate part of the outerside of the inserted nozzle 13. Due to the structure of the magneticforce device 16, a magnetic force can be applied to or removed from thenozzle 13 in a state with the neighborhood of the outside of each nozzle13 remaining stationary, by conducting or cutting off power to the coil19 serving as a magnetic source. Here, movement of the magnetic forcedevice 16 as well as the reservoir body 12 is controlled together by themoving mechanism for the reservoir body 12. The magnetic force device 16may be mounted in such a manner that it can be dismounted from thereservoir body 12.

A sliding body 20 is mounted above the reservoir body 12, and is capableof moving vertically relative to the reservoir body 12. The sliding body20 comprises a base plate 21, plural plungers 23 for sliding in thecylinders 11 and projecting downward from the base plate 21 and arrangedin a matrix and serving as sliding projections. The entire length of theplungers 23 is at least the same as or longer than depth of thecylinders 11.

The sliding body 20 comprises a mechanism (not shown in drawings), formoving vertically relative to the reservoir body 12. Such a mechanismmay be for example, a link mechanism, a cam mechanism, a ball screwmechanism, a stepping motor, or a DC motor etc. Here, the vessel 14 isdriven to move by a moving mechanism (not shown in the drawings) inrelation to the reservoir body 12, or by a stage on which the vessel 14is placed.

The apparatus 10 including such mechanisms may be installed into a framebody or a case body (not shown in the drawings). The frame body or thecase body may have a transfer mechanism for the vessels. Furthermore,the nozzles 13 may be formed to be separate from the reservoir body 12and fitted to the lower part of the reservoir body 12, instead of beingintegrated with the reservoir body 12. It is preferable that thereservoir body 12, the nozzles 13 and the vessel 14 are formed to betransparent or translucent so that the interior thereof can be seentherethrough. Moreover, O-rings may be mounted around the interiorcircumference of the upper part of the cylinders 11 for preventingleakage of liquid.

FIG. 2(a) is a schematic side view showing the whole apparatus accordingto the present embodiment.

The magnetic material used for the upper plate 18 a and the lower plate18 b etc. is a para-magnet such as iron (or a ferro-magnet with atemperature higher than the Curie temperature). Alternatively, an idealmagnetic force device free of residual magnetization can be obtained byusing a super para-magnet, which is the aggregate of minute particles offerro-magnet or anti-ferro-magnet materials (NiO, Fe₃O₄,Cr₂O₃ etc.). Theappropriate magnetic material is one such as Fe—Co alloy (49Co—2V—Fe)having a high saturation magnetic flux density and a high magneticpermeability.

As shown in FIG. 2(b), when the magnetic field is generated byconduction in the coil 19 of the magnetic force device 16, the upperplate 18 a is magnetized so as to have N polarity (or S polarity), andthe lower plate 18 b is magnetized so as to have S polarity (or Npolarity). Therefore, each wall part of the through sections being apartfrom one another can have opposite polarities respectively. Further, thenearest location between the upper plate 18 a and the lower plate 18 bis a gap 17 c between the tips of the projections 17 a, 17 b.

Therefore, since the heaviest concentration of the leakage of the linesof magnetic force is between the tips of the projections 17 a, 17 b, astrong magnetic field can be exerted on the nozzle 13, as shown in FIG.2(b).

Furthermore, FIG. 2(c) shows another example of a magnetic force device.For instance, the magnetic force device may comprise an upper plate anda lower plate, one or more (four in this example) pillars sandwichedbetween the plates and one or more (four in this example) electromagnetscomprising coils 191-194 having a wire wound around each pillar andconnected with a switch and a power source (not shown in the drawings).

Further, in this embodiment, the magnetic force device may be dividedinto four segments 161, 162, 163, 164 in such a manner that the coils191-194 can be included in each segment, respectively. Thus since auniform magnetic field can be applied over a vide range, the apparatuscan process a vessel having plural liquid containing parts.

FIG. 3 shows a cross-sectional view taken on line A—A in FIG. 1. Asshown in this figure, the tips of the plungers 23 projecting from thesliding body 20, are formed in a conical shape with a downwardlydisposed apex. Funnel parts 27 formed to be funnel-like are mounted insuch a manner that the plungers 23 come in contact with the funnel parts27 without a gap.

In the case of the measurement of light emission from the processedliquid accommodated in each liquid containing part 15 of the vessel 14,a light measuring device (not shown) in which light receiving componentsare arranged in a plane-like state, in a way to correspond to thelocation of each liquid containing part of the vessel, or lightreceiving components such as CCD elements are partitioned lattice-likeis used.

Since the light emission as a whole can be collectively caught as aplane image and the analysis of the light emission can be executedwithout time lag, results having the same conditions in time and highprecision can be obtained and the process can be swiftly and efficientlyexecuted.

FIG. 4 shows the assembled apparatus 10 according to the presentembodiment put to actual use.

In order to use the apparatus 10 according to the present embodiment, auser instructs a controller (not shown). Then a nozzle head of theapparatus 10 or a stage moves a vessel (not shown) accommodating theliquid incorporating the magnetic particles, so that the nozzles 13 drawthe suspension from the vessel collectively. Each nozzle 13 ispositioned to each liquid containing part 15 of the vessel 14corresponding to an object to be inspected or processed in a manner thatthe nozzle is located opposite the liquid containing part.

Then the suspension is discharged, to the specimens accommodated in theliquid containing parts and is collectively mixed with the specimens.Thus, each of the magnetic particles can be combined with the targetsubstances contained in the specimens. When the nozzle is withdrawnagain, the electromagnet is driven by passing current through the coil19, and the upper plate 18 a and the lower plate 18 b are magnetized tohave N polarity (or S polarity) and S polarity (on N polarity)respectively. Then the lines of magnetic force are generated along theupper plate 18 a, the lower plate 18 b and the pairs of projections 17a, 17 b, and leak out from the gaps 17 c.

Therefore, the magnetic field can be applied to the nozzles 13 placednear the gaps 17 c. The magnetic particles combined with the targetsubstances by adsorption or reaction with the substances coated with themagnetic particles or by direct adsorption to the surface of themagnetic particles, adhere to and are held to the inner wall of thenozzles 13. Thereafter, the residual liquid is discharged by loweringthe sliding body 20, while applying the magnetic field. Thus only themagnetic particles combined with the target substances can be separatedwithin the nozzles 13. Then the apparatus 10 per se or vessel on a stagemoves, so that each nozzle 13 is positioned with respect to each liquidcontaining part accommodating the necessary reagents. Thereafter,drawing and discharging are repeated in a state with the magnetic fieldremoved, and mixing with the reagents is executed by agitation in orderto execute an other process.

The target substances are processed by executing the above steps orrepeating the execution. When required, light emission is observed, thestrength of the light is measured or processed as an image by a lightmeasuring device (not shown), and the controller executes dataprocessing of the results, and the results of measurement are displayedon a monitor screen, or are recorded in a memory device.

SECOND EMBODIMENT

Next, an apparatus according to a second embodiment is shown in FIG. 5.

In FIG. 5, like elements are given the same reference numerals as thefirst embodiment. The sliding body 200 comprises a base plate 210, andplural plungers 230 projecting downward from the base plate 210,arranged in a matrix, sliding through the cylinders 11 and capable ofmoving to and from the reservoir body 12 vertically, and serving as thelarger diameter section of the sliding projections. Thin holes 22penetrate the base plate 210 and the plungers 230 vertically. A minutesliding body 24 is mounted above the sliding body 200 with projectingdownward plural thin rods 25 sliding through the thin holes 22 and thenozzles 13 and serving as the small diameter section, and capable ofmoving vertically to and from the sliding body 200.

The entire length of the thin rods 25 is at least the same as or longerthan the entire depth of the thin holes 22 and the entire length of thenozzles 13.

Such minute quantities of liquid that are hard to handle by moving onlythe sliding body 200 vertically, can be handled and processed by movingthe minute sliding body 24 vertically with high precision. Liquid andresidual substances remaining in the nozzles 13 can be completelyprecluded.

Mechanisms (not shown) for vertical movement and horizontal movement aremounted on the sliding body 200 and the minute sliding body 24respectively. Such mechanism may be for example, a link mechanism, a cammechanism, a ball screw mechanism, a stepping motor, or a DC motor.These mechanism and the apparatus may be installed in a frame body orenclosed in a box (not shown).

Further, a transfer mechanism may be mounted in the frame body or thebox body. Instead of being a single-piece construction, the nozzles 13may be formed to be separate from the reservoir body 12. An O-ring maybe mounted along the interior circumference of the upper part of thecylinder 11 for preventing leakage of liquid therefrom.

FIG. 6 shows a cross-sectional view taken on line B—B of FIG. 5 of theassembled apparatus 110 according to the present embodiment. In the casewhere a comparatively larger amount of liquid is processed, drawing anddischarging are executed by sliding the sliding body 200 and the minutesliding body 24 vertically with the tip of the plunger 230 of thesliding body 200 and the tip of the thin rods 25 of the minute slidingbody 24 coinciding.

On the other hand, in the case where a minute amount of fluid is drawnor discharged with high precision, the plungers 230 are lowered to thelowest ends of the cylinders 11 together with the sliding body 200, andonly the thin rods 25 of the minute sliding body 24 are further allowedto slide through the nozzles 13 for drawing or discharging. Furthermore,the tips of the thin rods 25 can be moved up to the tips of the nozzles13 or to penetrate through the nozzles 13 to the outside.

THIRD EMBODIMENT

Next, an apparatus 30 according to a third embodiment, is described onthe basis of FIG. 7.

The apparatus 30 according to the present embodiment is used forprocesses for minute amounts of liquid. As shown in FIG. 7, theapparatus comprises a plank-like reservoir body 32 mounted with pluralpit-like cylinders 31 arranged in a matrix, serving as pluralreservoirs.

Under the reservoir body 32, plural nozzles 33 communicating with thecylinders 31 are formed to be integral with the reservoir body 32 and tobe projecting downwards from the reservoir body 32. The size andthickness of the nozzles 33 are determined so that the nozzles 33 can beinserted into liquid containing parts 35 provided in a vessel 34 placedunder the apparatus, and have a capacity larger than that of the liquidcontaining parts 35.

In the apparatus 30 according to the present embodiment, the cylinders31 communicate with the nozzles 33, and the inside diameter of thecylinders 31 is the same to that of the nozzles 33. The inside diameterof the cylinders 31 and the nozzles 33 is for example, the order of afew mm (about 6 mm in this example).

A transfer mechanism (not shown) is mounted on the reservoir body 32 sothat the reservoir body 32 can move to and from the vessel 34 verticallyand horizontally. A magnetic force device 36 is mounted, under thereservoir body 32 and above the vessel 34. The magnetic force device 36comprises plural through sections 37 arranged in a matrix correspondingto the location of the nozzles 33, which have wall parts being incontact with or near the outside of the inserted nozzles 33 and capableof being magnetized and demagnetized. The structure of the magneticforce device 36 is the same to that of the one described in the firstembodiment, except for the diameter of the through sections and so on.Above the reservoir body 32, a sliding body 40 capable of moving to andfrom the reservoir body 32 vertically, is mounted. The sliding body 40comprises plural plungers 43 serving as sliding projections, whichproject downwardly from the sliding body 40 and can slide through thecylinders 31. The entire length of the plungers 43 is preferablydetermined to be the same as or longer than the sum of the depth of thecylinders 31 and the length of the nozzles 31.

Further, the sliding body 40 comprises a mechanism (not shown) formoving to and from the reservoir body 32 vertically. Here, in FIG. 7,reference numeral 38 indicates magnetic particles, reference numeral 39indicates a liquid which is an object for the process. Further,reference numeral 41 indicates an interior circumferential groove, andreference numeral 42 indicates an O-ring fitted into the groove.

This embodiment is suitable for the case where an amount of liquid iscomparatively small and the capillary-like nozzles and the cylinders,being the reservoir, have a small capacity. The cylinders 32, thenozzles 33 and the vessel 34 are preferably formed to be transparent sothat the inside can be seen therethrough.

FOURTH EMBODIMENT

Next, an apparatus 50 according to a fourth embodiment is described, onthe basis of FIG. 8.

The apparatus 50 according to the present embodiment, comprises aplank-like reservoir body 52 where plural pit-like cylinders 51 servingas plural reservoirs, are arranged in a matrix. Plural nozzles 53communicating with each cylinder 51 are stuck to the lower part of thereservoir body 52, by welding and so on in such a manner that pluralnozzles project from the reservoir body 52 downwards.

The length and the thickness of the nozzles 53 are determined so thatthe nozzles 53 can be inserted into the plural liquid containing parts55 mounted in the vessel 54 placed under the apparatus 50, and can havea capacity sufficiently large to be that of the liquid containing parts55. With the apparatus according to the present embodiment, the innerdiameter of the cylinders 51 is different from that of the nozzles 53.The apparatus 50 is suitable for processes for liquids of amounts largerthan that handled by the apparatus 30 according to the third embodiment.

A mechanism (not shown) is mounted so that the reservoir body 52 and thevessel 54 can move to and from each other vertically or horizontally.

A magnetic force device 56 is mounted below the reservoir body 52 andabove the vessel 54. The magnetic force device 56 comprises pluralthrough sections 57 arranged in a matrix and corresponding to thelocations of the nozzles 53, with wall parts being in contact with ornear the outside of the inserted nozzles 53 and capable of beingmagnetized and demagnetized. The magnetic force device 56 is the same tothat of the first embodiment except for the diameter of the throughsections.

Above the reservoir body 52, a sliding body 60 capable of moving to andfrom the reservoir body 52 vertically, is mounted. The sliding body 60comprises plural plungers 63 which project downwardly from the slidingbody 60 and can slide through the cylinders 51, serving as slidingprojections. The entire length of the plungers 63 is preferablydetermined to be shorter than the depth of the cylinders 51 so that anair layer can be formed between the tips of the plungers 63 and theliquid to be drawn or discharged.

Further, the sliding body 50 comprises a mechanism (not shown) formoving vertically. Here, reference numeral 61 indicates an interiorcircumferential groove, and reference numeral 62 indicates an O-ringfitted into the groove 61 for preventing leakage of liquid.

FIFTH EMBODIMENT

Next, an apparatus 70 according to, a fifth embodiment is described onthe basis of FIG. 9. As shown in FIG. 9, the apparatus 70 according tothe present embodiment comprises a plank-like reservoir body 72 arrangedwith plural pit-like cylinders 71 in a matrix, serving as pluralreservoirs.

Under the reservoir body 72, plural nozzles 73 communicating with thecylinders 71 are mounted in such a way that the plural nozzles 73project downwards from the reservoir body 72. Each nozzle 73 is fittedinto the lower part of each cylinder 71 in a manner that the nozzles 73can be detached.

A pushing body 78 is mounted above the reservoir body 72. The pushingbody 78 comprises plural pushing pipes 79 which project downward from abase plate 81 of the pushing body 78, are in contact with the upperparts of the nozzles 73 within the cylinders 71 and are inserted intothe cylinders 71 from the upper parts of the cylinders 71 so that thenozzles 73 can be pushed out of the cylinders 71.

Plural thin holes 82 vertically penetrate the base plate 81 and thepushing pipes 79 of the pushing body 78. An interior circumferentialgroove 87 is provided in each of the thin holes 82, and an O-ring 88 isfitted into the groove 87 so as to prevent leakage of liquid from thethin holes 82.

Further, interior-circumferential grooves 85 a, 85 b are provided ineach cylinder 71, and O-rings 83 a, 84 b are fitted into the grooves 85a, 85 b for securely holding the nozzles 73, respectively. Further, theO-rings 84 a serve for preventing leakage of liquid between the nozzles73 and the cylinders 71, and the O-rings 84 b serve for preventingleakage of liquid between the pushing pipes 79 and the cylinders 71. Amechanism (not shown) is mounted so that the reservoir body 72 can moveto and from the vessel 74 having the liquid containing parts 75,vertically and horizontally.

A magnetic force, device 76 is mounted under the reservoir body 72 andabove the vessel 74. The magnetic force device 76 comprises pluralthrough sections 77 having wall parts being in contact with or near theoutside of the inserted nozzles 73 and capable of being magnetized anddemagnetized, and arranged in a matrix in a manner corresponding to thelocation of the nozzles 73 of the reservoir body 72.

A sliding body 80 is mounted above the reservoir body 72, in a mannerthat the sliding body can move to and from the reservoir body 72,vertically. The sliding body 80 comprises plural plungers 83 thatproject downwardly from the sliding body 80 and can slide through thethin holes 82 and the nozzles 73.

The entire length of the plungers 83 is preferably determined to be thesame as or longer than the sum of the depth of the thin holes 82 and thelength of the nozzles 73.

With the present embodiment, liquid can be drawn from or discharged tothe liquid containing parts 75 of the vessel 74, by moving the slidingbody 80 vertically. Further, the pushing body 78 is mounted on theapparatus 70. Since the pushing pipes 79 are mounted in contact with thenozzles 73 within the cylinders 71, the nozzles 73 can be detached bymoving the pushing body 78 downward. Here, a mechanism (not shown) ismounted for moving the sliding body 80 and the pushing body 78vertically. The pushing body 78 may be moved only downward by hand.

SIXTH EMBODIMENT

Next, the apparatus 90 according to a sixth embodiment is described onthe basis of FIG. 10. As shown in FIG. 10, the apparatus 90 according tothe present embodiment comprises a plank-like reservoir body 92 arrangedwith plural cylinders 91 in a matrix. Each cylinder 91 of the reservoirbody 92 is equipped with a nozzle 93 in a manner that the nozzle 93 isinserted into the cylinder 91 and projects from the reservoir body 92downward. The length and the diameter of the nozzles 93 are determinedso that the lower parts 109 of the nozzles 93 can insert into pluralliquid containing parts 95 provided in the vessel 94 placed under theapparatus 90 and have a capacity large enough to store the contents ofthe liquid containing parts 95. Further a moving mechanism (not shown)is mounted in such a manner that the reservoir body 92 can move to andfrom the vessel 94 vertically and horizontally. A magnetic force device96 is mounted under the reservoir body 92 and above the vessel 94. Themagnetic force device 96 comprises plural through sections 97 havingwall parts being in contact with or near the outside of the insertednozzles 93 and capable of being magnetized and demagnetized, andarranged in a matrix in a manner corresponding to the location of thenozzles 93. The magnetic force device 96 is the same as the oneaccording to the first embodiment except for the diameter of the throughsections and so on.

As exemplified in FIG. 11, a circumferential lip part 98 is mountedaround the periphery of the nozzle 93 which is inserted into the throughsection 97 of the magnetic force device 96, and is exposed below themagnetic force device 96, for detaching the nozzle 93.

Further, as shown in FIG. 10, a stroke-down plate 99 is mounted betweenthe lip parts 98 and the lower surface of the magnetic force device 96.The stroke plate 99 comprises plural small hole parts 101 having adiameter that is larger than that of the nozzles 93 and smaller thanthat of the lip parts 98, and take insertion of the nozzles 93.

A sliding body 100 is mounted above the reservoir body 24, in a mannerthat the sliding body 100 can move to and from the reservoir body 92,vertically. Plural plungers 103, serving as plural sliding projections,project downward from the sliding body 100 and can slide inside thenozzles 93. The entire length of the plungers 103 is preferablydetermined to be the same as or smaller than the length of the nozzles93.

As shown in FIG. 10, an interior circumferential groove 105 is providedin each of the cylinders 91, and an O-ring 104 is fitted into the groove105 for securely holding the nozzle 93 and preventing leakage of liquid.Similarly, interior circumferential grooves 115 are provided, andO-rings 114 are fitted into the grooves 115 for preventing leakage ofliquid from openings between the plungers 103 and the cylinders 91.

As shown in FIGS. 10 and 11, it is preferable that beveling is executedat an edge of an opening 106 in the upper part of each nozzle 93, sothat the nozzles 93 can be easily inserted into the cylinders 91. Fromthe same reason, it is preferable that beveling is executed at an edgeof an opening 107 in the lower part of each cylinder 91 and an edge ofan opening 108 in the lower part of each through section 97.

Further, a mechanism (not shown) for moving the sliding body 100vertically is provided. In order to detach the nozzles 93 from thereservoir body 92, the lip parts 98 can be pulled out downward by movingthe stroke-down plate 99 downwards and catching the lip parts 98 withthe small hole parts 101.

SEVENTH EMBODIMENT

Next, a method of controlling an apparatus according to a seventhembodiment is described on the basis of FIG. 12.

In the present embodiment, four bases constituting DNA, namely A(adenine), G(guannine), T(thymine), C(cytosine) or four basesconstituting RNA, namely A (adenine), G(guannine), R(uracil),C(cytosine) are used as elements of substances. The integrated processfor generating combined substances having structures of base sequencesof seven bases which are arbitrarily combined with each other are shownon the basis of FIG. 12. Necessary equipment used for this process isfor example, the apparatus arranged with nozzles in a matrix of 64rows×64 columns, a multi-nozzle device with 64 multi nozzles 131, 132,133 134, and seven kinds of vessels 141-147 having liquid containingparts arranged in a matrix of 64 rows×64 columns.

As shown in FIG. 12, at step S1, liquids incorporating each base aredispensed into each liquid containing part of each vessel (reagentplate) 141-147 by using the multi nozzle apparatus 131, 132, 133, 134,in a row-like state or a column-like state of having predeterminedwidths shown in the figure (one, four, sixteen). Here, magneticparticles serving as carriers, may be dispensed and disposed beforehand,before dispensing the liquids incorporating the base.

At step S2, the nozzles of the apparatus for an integrated process arepositioned on the vessels (not shown) accommodating the suspensionincorporating the magnetic particles in such a manner that each nozzlefaces each liquid containing part, by transferring the apparatus, thedevices or the stage on which the vessel is placed. Then, the magneticforce device is driven so that the magnetic field is applied to thenozzles all together, while drawing the specimens. Therefore, themagnetic particles adhere to and are held on the inner walls of thenozzles. Thereafter, the residual liquid after the magnetic particleshave been captured and separated, is discharged to the vessels alltogether. While the apparatus holds the magnetic particles, theapparatus or the stage is transferred to a place over the vessel 141whose liquid containing parts accommodate a liquid incorporating A-baseand is positioned in such a manner that each nozzle faces each liquidcontaining part. After the nozzles of the apparatus are inserted intothe liquid containing parts, the magnetic force device demagnetizes thewall parts all together.

On this occasion, generation of residual magnetization may be preventedby reversing the direction of the magnetization with a strength ordriving time according to the strength or driving time immediatelybefore demagnetization. Thereafter, the magnetic particles areresuspended in the liquid by drawing and discharging a suspensionincorporating A base accommodated in the vessel 141 all together withthe drawing/discharging devices of the apparatus. The apparatus mixesand agitates both suspensions by repeating drawing and discharging. Asubstance for combining A-base with the magnetic particles is coated onthe surface of the magnetic particles beforehand.

The A-base combines with the surface of the magnetic particles, byagitating and mixing. In order to combine the surface of the magneticparticle 38 with only one A-base, the speed, time, number of times ofdrawing and discharging or predetermined reagents may be controlled.

Thereafter, the apparatus drives the magnetic force device to apply themagnetic field to the nozzles, all together again so that the magneticparticles combined with A-base can adhere to the inner walls of thenozzles and be captured and separated, while the drawing/dischargingdevice draws the entire amount of the suspension from the vessel 141.Then, the accumulation of residual magnetization may be prevented bycanceling the magnetization by reversing the direction of magnetizationwith respect to the immediately previous direction thereof The residualliquid after the magnetic particles have been separated, is dischargedfrom the nozzles of the apparatus in a state with the magnetic fieldapplied to the nozzles.

At step S3, the apparatus or the stage on which the vessel is placed istransferred horizontally to the vessel 142 in a state with the magneticparticles adhering to the inner walls of the nozzles. Then each nozzleof the apparatus for an integrated process is positioned so that eachnozzle faces each liquid containing part of the vessel 142. As show inthe figure, each base, A, G, T, C is dispensed in each group of 16 rowsof liquid containing parts beforehand. The nozzles are inserted into theliquid containing parts by lowering the nozzles of the apparatusdownward all together, and the magnetic force device is demagnetized alltogether.

On this occasion, the demagnetization may be executed after reversingthe direction of magnetization, in a manner to cancel the residualmagnetization. Thereafter, the magnetic particles are resuspended in theliquid by drawing and discharging each suspension incorporating each A-,B-, C-, D-base respectively, all together. Each base is combined witheach A-base having already combined with the magnetic particles.Consequently, as shown in step S3 in FIG. 12, each base sequence such asA-A, A-G, A-T, A-C is obtained.

Thereafter, the apparatus drives the magnetic force device to apply themagnetic field to the nozzles, to make the magnetic particles adhere tothe inner walls of the nozzles and capture and separate the magneticparticles, while drawing the whole suspension from the vessel 142. Onthis occasion, the residual magnetization maybe prevented by reversingthe direction of the magnetization with respect to that of themagnetization at the previous step S2.

The residual liquid after the magnetic particles are separated, isdischarged from the nozzles of the apparatus while the magnetic field isapplied to the nozzles.

The following processes at step S4 and step S5 are the same as theprocess at step S3, except that the arrangement of the base dispensedbeforehand is different from that of step S3 in vessels 143, 144 of FIG.12. On this occasion, the direction of magnetization may be reversedwith respect to that of the immediately prior magnetization, forpreventing residual magnetization. Thus, at step S4, base sequences suchas A-A-A and A-A-G are obtained as shown in step S4 of FIG. 12. Atstep S5, base sequences such as A-A-A-A and A-A-A-G are obtained, asshown in step S5 in FIG. 12.

At step S6, in a state with the magnetic particles adhering to the innerwall of the nozzles, the apparatus or the stage on which the vessel isplaced is transferred horizontally and rotated through 90° with avertical axis (transposing movement) so that the nozzles of theapparatus are positioned over the vessel 155. Consequently, as shown instep S6 in FIG. 12, dispensing and mixing are executed in a transposedarrangement of elements of substances with respect to that at stepsS3-S5.

The following process is the same to that of step S3. As a result, asshown in step S6 in FIG. 12, such base sequences as A-A-A-A-A can beobtained in the magnetic particles. Similarly, as shown in step S8 inFIG. 12, such base sequences as A-A-A-A-A-A can be obtained by goingthrough the processes at steps S7 and S8.

By the above processes at steps S1-S8, 4⁶=4086 kinds of base sequencesof seven bases can be obtained. When these processes at steps S1-S8 areexecuted in the vessel 141, for G, T, C, instead of A-base, 4⁷=16384kinds of base sequences of seven bases can be obtained in total.

Though only the case of DNA is mentioned, in the above embodiments, RNA,integrated generation of combined substances obtained by the arbitrarycombination of elements of substances such as three, five, or ten kindsof amino acids and so on is possible. Further, on the way to thereaction plates, various operations such as cleaning or activation forreaction can be arbitrarily combined. Further, the generation of theabove combined substances is executed by using the magnetic particlesserving as a carrier, and the apparatus. However, the method ofgeneration is not limited to this case. Instead of using the apparatus,the generation can be executed by using a vessel or column clusterhaving a function of capturing the magnetic particles. In this case,such a magnetic force device as can apply and remove the magnetic forcein a state that the neighborhood of each liquid containing part in thevessel or column remains stationary, can be used instead of keeping theneighborhood of the nozzles stationary.

Furthermore, instead of the magnetic particles, non-magnetic particlessuch as high polymer particles, and a vessel or column cluster having afunction of capturing the non-magnetic particles may be used.

Though in the above cases the nozzles and liquid containing parts, andthe sliding projections etc. are arranged in a matrix of predeterminedsize, the invention is not limited to these cases. For example, furtherlarger sizes such as 384 items (16 rows×24 columns) may be arranged in amatrix, or these may be arranged in such a close state that eachneighboring row or neighboring column is alternately shifted one to theother, or these may be arranged cartridge-like in a row or a column ormay be arranged, circularly, annular ring-like, radially, orpolygon-like.

The shape of the reservoir body or vessel is not limited toquadrilateral but may be square or circular. When the reservoir body andthe nozzles are made of a transparent body or a translucent body, theinside can be seen therethrough, conveniently. The shape of the nozzleor cylinder part is not limited to being cylindrical, but may be asquare pillar or cone shape etc.

Here, the apparatus according to each embodiment comprises a controller(not shown). The controller comprises an input means such as a keyboard,a mouse, a CD driver, a floppy disc driver, an IC card of the protocolcontrol method, a touch panel, or a communicating device, a data storingunit for storing programs or data such as a memory, a CD, or a floppydisc, a CPU for executing various instructions on the basis ofinstructions, programs or data, a display unit for displaying variouscontents, an outputting device for outputting results of processes,results of measuring, results of experiments, such as a printer, agraphic device, a communicating device, a CD, a floppy disc, and adriving controller for controlling the driving of various mechanisms onthe basis of CPU instructions. In short, the apparatus according to thepresent, invention is equipped with various devices necessary forcontrol. Another example of the magnetic force device is shown in FIG.13.

EIGHTH EMBODIMENT

As shown in FIG. 13(a), a magnetic force device 165 according to aneighth embodiment comprises an upper plate 185 a and a lower plate 185 bwhich are mounted oppositely at a predetermined interval, made of anon-magnetic material such as resin, and plural pillars 175 a sandwichedbetween the two plates 185 a, 185 b and connecting between the plates,made of a magnetic or non-magnetic material. At each pillar 175 a, athrough section 175 capable of taking insertion of a nozzle 13 isprovided in a manner penetrating the plates 185 a, 185 b vertically. Theoutside of each pillar part 175 a is provided with a coil which is woundby a wire 195 in a manner that the through section 175 is enclosed. Thewire 195 constitutes the electromagnet capable of generating andextinguishing a magnetic field by connecting with a switch and a powersource (not shown). By the present structure, since a magnetic field canbe generated at point blank range of the nozzle 13, a strong magneticfield can be generated. Further, since the coil is not mounted on thenozzle, the nozzle per se can be disposed.

The wire 195 may be separate in each through section 175, or may becommonly used with plural through sections or with all through sections.

Here, each pillar part 175 a may be mounted separate from the upperplate 185 a and the lower plate 185 b, or may be mounted integral witheither the upper plate 185 a or the lower plate 185 b. In these cases,after the coils are fitted, the coils are fixed by securing with thelower plate 185 b or the upper plate 185 a.

NINTH EMBODIMENT

A magnetic force device 166 according to a ninth embodiment, shown inFIG. 13(b) comprises a plank plate made of a magnetic body, and thethrough section is through holes 176 provided in the plank plate andcapable of taking insertion of the nozzles. In this case, the magneticfield is applied by the magnetic source 196, not vertically buthorizontally. FIG. 13(c) is a cross-sectional view of the magnetic forcedevice.

Thus, the structure of the magnetic force device can be simplified. Inthis case, as shown in FIG. 13(d), by using a magnetic force device withpiled up thin plates of magnetic materials (normal direction of theplate may be vertical or horizontal), a uniform magnetic field can beapplied without leakage of the magnetic field.

TENTH EMBODIMENT

As shown in FIG. 13(e), a magnetic force device 167 according to a tenthembodiment applies a magnetic field from left to right in the drawings,being different from the aforementioned first embodiment. A gap 177 a isformed in a manner penetrating each through hole 177 perpendicularly inthe drawings. The wall part of each through hole 177 is thus dividedinto left and right and the gap 177 a has the shortest distance withinthe magnetic force device and each divided wall part has oppositepolarities.

ELEVENTH EMBODIMENT

As shown in FIG. 13(f), a magnetic force device 168 according to aneleventh embodiment applies a magnetic field from left to right in thedrawings. A gap 178 a is formed in a manner that the wall part of eachthrough hole 178 is divided perpendicularly into right and left, and hasthe shortest interval within the magnetic force device and each wallpart has opposite polarities. Magnetic sources 198 are mounted on bothsides.

Thus, strong magnetic fields can be applied to the nozzle in eachthrough section with a simplified structure. Here, in FIG. 13(e) andFIG. 13(f), the division into up and down and the division into rightand left may be combined in a way that the magnetic force is alsoapplied perpendicularly in the drawings.

TWELFTH EMBODIMENT

In FIG. 13(g), a magnetic force device 169 according to a twelfthembodiment is shown. The magnetic force device 169 comprises pluralmagnetic segments (for example, corresponding to rows of nozzlesselected from the plural nozzles arranged in a plane-like state) whichare divided so that each segment has a size large enough to maintain thenecessary strength of the magnetic force therein.

THIRTEENTH EMBODIMENT

A magnetic force device 306 etc. according to a thirteenth embodiment isshown in FIG. 14(a).

The magnetic force device 306 comprises electromagnets (or permanentmagnets) 309 serving as a magnetic source, two sheets of magnetic plates308 a, 308 b connecting with the electromagnets, facing up and down at apredetermined interval, and capable of magnetization and demagnetizationand made of magnetic material, and plural through sections 307penetrating the two sheets of the magnetic plates 308 a, 308 bvertically and capable of taking insertion of the nozzles 303.

Further, each through section 307 comprises a pair of projections 304,305 made of magnetic material. The pair of projections 304, 305 projectin opposite directions to one another, towards the opposite surface, andeach tip of the projections 304, 305 is apart from each opposite surfaceat a first interval “A”, and the tips of the projections 304, 305 areapart from one another at a second interval “B”, and each projection hasan opposite polarity to the other. Reference numeral 302 indicates thereservoir body, and reference numeral 301 indicates the reservoirs. Thepair of projections 304, 305 correspond to the divided parts of thenozzle outer member.

With the magnetic force device 306 according to the present embodiment,the second interval “B” is formed to be shorter than the first interval“A”. Consequently, lines of magnetic force or flux lines are formedbetween the tips of the projections 304, 305 more densely than thoseformed between the tips of the projections and the magnetic plates 308a, 308 b. Consequently, a strong magnetic field can be applied to thenozzles 303 horizontally.

FIGS. 14(b)(c) shows the through holes 310 a, 310 b whose openings areenlarged by removing opposite areas near each tip of projections 304,305 in each magnetic plate 308 a, 308 b. In this case, the firstinterval “A” between each projection 304, 305 and the opposite area islengthened to be longer than the second interval “B”, and more lines ofmagnetic force or more dense flux lines can pass through the secondinterval “B”. In this example, the size of the opening of each throughhole 310 a, 310 b may be formed to be equal to the other, and theposition of the center of each hole may be shifted sufficiently so thatthe tip of the nozzle can pass through the two holes.

FOURTEENTH EMBODIMENT

Next, a magnetic force device 316 according to a fourteenth embodiment,is described on the basis of FIGS. 15(a), (b), (c). As shown in FIG.15(a), the magnetic force device 316 according to the present embodimentcomprises, a magnetic source 317, two sheets of magnetic plates 318 a,318 b mounted in face-to-face relationship at a predetermined intervaland made of magnetic material capable of being magnetized anddemagnetized, and plural through sections 320 penetrating the two sheetsof the magnetic plates 318 a, 318 b vertically, and capable of takinginsertion of the nozzles and arranged in a matrix.

A magnetic source 317 is mounted out of the space sandwiched by themagnetic plates 318 a, 318 b. The magnetic source 317 comprises magneticelements 317 a, 317 b, 317 d, and a coil 317 c. The magnetic elements317 a, 317 b, 317 d comprise a first part 317 a, a second part 317 b,and an iron core 317 d being mounted with a coil 317 c, which are formedseparate to each other. An end of the first part 317 a connects with themagnetic plate 318 a, an end of the second part 317 b connects with themagnetic plate 318 b, and the other end of the first part 317 a and theother end of the second part 317 b connect with each end of the ironcore 317 d mounted with the coil 317 c and are fixed by screws or thelike.

The magnetic elements 317 a, 317 b, 317 d and the both edges of themagnetic plates 318 a, 318 b that are not faced each other at the edges,are formed to be horseshoe-like as a whole. Reference numeral 319indicates a spacer made of a non-magnetic body and mounted between themagnetic plate 318 a and the magnetic plate 318 b.

FIG. 15(b) is a side view of the magnetic force device 316 shown in FIG.15(a). In each through section 320 of the magnetic force device 316, asshown in FIG. 15(b), a pair of projections 322 a, 322 b are mounted,which project toward the facing surface of the magnetic plates 318 a,318 b respectively, and are made of magnetic material, and whose tipsare apart from each other.

As shown sectionally with the enlarged upper part of FIG. 15(c), at eachposition of the pair of the projections, a hole penetrates the magneticplates 318 a, 318 b and the pair of projections 322 a, 322 b vertically,so that the nozzle can be inserted therein.

The lower part of FIG. 15(c) is an enlarged sectional view of a pair ofprojections according to an other example. The pair of the projections323 a, 323 b project from the magnetic plate of the opening edge of thethrough section toward the facing surface in the opposite direction toeach other. The tips of the projections are apart from the facingsurface at a first interval A respectively, and are apart from eachother separated from the nozzle 321 at a second interval “B” shorterthan the first interval, in such a manner that they have oppositepolarities by magnetization, respectively.

With the present embodiment, since the magnetic source 317 is mountedoutside of the space sandwiched by the magnetic plates 318 a, 318 b, theturn number of wound wire of the coil 317 is not restricted by theinterval between the two magnetic plates 318 a, 318 b. With theembodiment, the amount of wire wound on the coil 317 c can be increased,according to the width of the magnetic plates 318 a, 318 b and thelength of the magnetic elements 317 a, 317 b. Further, plural coils maybe mounted in parallel, in the magnetic force device. Consequently, astrong magnetic field can be provided, without extending the intervalbetween the two magnetic plates.

Though in the present embodiment, the first part 317 a, the second part317 b and the iron core 317 d are described as being separate to eachother, the magnetic elements 317 a, 317 b and 317 d may be formed to bein one piece, or further may be formed to be in one piece together withthe magnetic plates 318 a, 318 b. In the case where they are formed tobe separate to each other, production can be facilitated because theycan be divided into a simple form, in comparison to the case where theyare formed to be in one piece. Further, the coil may be formed bywinding wire around the overlapped ends of the first part and the secondpart.

Though the magnetic force devices according to the present embodiment,shown in FIGS. 15(a), (b), (c) are described for the case where only onemagnetic source is mounted, as shown in FIG. 16, two magnetic sources325, 327 may be mounted outside of the space sandwiched by the, magneticplates 328 a, 328 b and both sides of the magnetic plates 328 a, 328 b,in such a manner that the axes of the magnetic sources 328 a, 328 b arefacing each other and in a horizontal plane with the plane parallel withthe magnetic plates 328 a, 328 b. As described in FIG. 15, each magneticsource 325, 327 comprises coils 325 c, 327 c, and magnetic elements 325a, 325 b, 325 d, and 327 a, 327 b, 327 d, respectively. The magneticelements comprise first parts 325 a, 327 a, second parts 325 b, 327 b,and iron cores 325 d 327 d wound by the coils 325 c, 325 c which areformed to be separate to each other. Ends of the first parts 325 a, 327a connect to the magnetic plate 328 a with the magnetic plate 328 adiagonally therebetween, and other ends of the second parts 325 b, 327 bconnect to the magnetic plate 328 b with the magnetic plate 328 bdiagonally therebetween.

The other ends of the first parts 325 a, 327 a and the other ends of thesecond parts 325 b, 327 b connect to each end of the iron cores 325 d,327 c wound by the coils 325 c, 327 c, and are fixed by screws or thelike.

Here, the magnetic plates 328 a, 328 b as well as the magnetic plates318 a, 318 b are disposed in plane-parallel face-to-face relationship ata predetermined interval and are made of a magnetic material capable ofmagnetization and demagnetization. Plural through sections 329 capableof taking insertion of the nozzles, penetrate the two magnetic plates328 a, 328 b vertically. Further, the structure of each through section329 is the same as the one shown in FIG. 15(c). With the presentembodiment, a stronger magnetic field can be supplied in comparison tothe one having a single magnetic source. Here, though the ,embodimentwith two magnetic sources is described, a plurality of magnetic sources,such as three or four magnetic sources used in a like manner also fallswithin the scope of the present invention.

FIFTEENTH EMBODIMENT

A magnetic force device 330 according to a fifteenth embodiment is shownin FIG. 17. The magnetic force device 330 according to the fifteenthembodiment, is used in the case where the nozzles comprise a pipette tipcapable of being mounted and dismounted. The magnetic force device 330according to the fifteenth embodiment, enables the pipette tip to beinserted into or detached from the through section 331 of the magneticforce device 330 without cross contamination.

As shown in FIG. 17(a), the magnetic force device 330 comprises anelectromagnet (or a permanent magnet) serving as a magnetic source (notshown), two magnetic plates 331 a, 331 b magnetically connected to theelectromagnet, mounted in face-to-face-relationship at a predeterminedinterval, in the low and high positions, respectively, and made of amagnetic material capable of magnetization and demagnetization, pluralthrough sections 332 penetrating the two magnetic plates 331 a, 331 bvertically and capable of taking insertion of the pipette tips servingas the nozzles. The number of through sections 332 is the same as ormore than that of the pipette tips of the apparatus. When the connectingrelation between the magnetic source (not shown) and each magnetic plate331 a, 331 b is such as shown in FIG. 15, the magnetic plate 31 a ismagnetized for example to have N polarity, and the magnetic plate 331 bto have S polarity.

FIG. 17(c) is a plan view of the through section 332. A cross-sectionalview taken on line X-X′ of FIG. 17(c) is shown in FIG. 17(b). Eachthrough section 332 comprises a separate hole 333 whose nozzle outermember is in contact with or near the periphery of the pipette tip whenthe pipette tip serving as the nozzle is inserted therein, and aninsert-withdraw hole 334 mounted adjacent to the separate hole 333 andcapable of horizontal transfer of the pipette tip to and from theseparate hole 333 and having an opening larger than that of the separatehole, for inserting and detaching the pipette tip.

The nozzle outer member of the separate hole 333 is a pair ofprojections 333 a, 333 b which project toward the facing surface of themagnetic plates 331 a, 331 b near the opening of the separate hole 333,made of a magnetic material and can take insertion of the pipette tipand are formed to have a somewhat “C” shaped transverse cross-sectionand a cylindrical configuration, and the tips of which are apart fromeach other.

The projections 333 a, 333 b do not enclose the sides of the pipette tipcompletely, so that an opening capable of passing the pipette tiptherethrough is formed for joining with the insert-withdraw hole 334spatially. In this case, the projections 333 a, 333 b may be formed soas to be integral with the magnetic plates 331 a, 331 b, or may beformed so as to be separate from each other and so as to be fitted intoholes formed in the magnetic plates 331 a, 331 b.

The reason for providing the insert-withdraw hole 334 as well as theseparate hole 333, is as follows:

Liquid adhering to the lower peripheral part of the pipette tip whichcomes in contact with the accommodated liquid, will contaminate themagnetic force device 330 by coming in contact with the separate hole333 or the projections 333 a, 333 b while withdrawing the tip from thethrough section 331, or the liquid adhering to the contaminated separatehole 333 etc. may contaminate the newly equipped pipette tip by comingin contact with the pipette tip while inserting the tip into the throughhole 331. Consequently, withdrawal or insertion is executed through ahole that has a larger diameter than that of the periphery of thepipette tip in order to prevent such cross contamination.

FIGS. 17(d), (e) shows another example of the through section of themagnetic force device. In this example, the through section 332comprises a pair of projections 337 a, 337 b. The pair of projectionsproject toward the facing surfaces from the magnetic plates 336 a, 335 bat the edge of the opening of the through section 332 in oppositedirections respectively, and are made of magnetic material and arespaced apart from one another in a manner so as to have oppositepolarities by magnetization. The tips of the pair of projections areapart from the facing surface at a first interval “A”, and are apartfrom one another at a second interval B shorter than the first interval.The magnetic plates 335 a, 335 b in the parts facing the projections,may be removed in order to extend the interval “A” further.

SIXTEENTH EMBODIMENT

Next, a magnetic force device 353 according to a sixteenth embodiment isdescribed on the basis of FIG. 18. In the apparatus according to thepresent embodiment, plural nozzles are mounted in the reservoir body 350that constitutes the drawing/discharging device. The nozzles eachcomprise a fitting part 351 and a pipette tip 321 fitted to the lowerpart of the fitting part 351 in a way that the pipette tip 321 can bedetached. The tip 321 comprises a two-step structure comprising a smalldiameter section and a larger diameter section. A magnetic force device353 is mounted under the reservoir body 350. FIGS. 18(a)(b) shows tipracks 357, 358 mounted under the magnetic force device 353 for thefitting and detaching of the pipette tips, and FIGS. 18(c)(d) shows amicroplate 361 having 96 wells (liquid containing parts, 8 rows×12columns) for drawing or discharging.

In regard to the magnetic force device 353, plural through sections 354capable of taking insertion of each tip 321 are mounted in a way so asto penetrate the two magnetic plates 353 a, 353 b. The magnetic plates353 a, 353 b are magnetically connected to the electromagnet or can bemagnetically connected to a permanent magnet, serving as a magneticsource (not shown) respectively. Each magnetic plate 353 a, 353 b ismagnetized in a way so as to have opposite magnetic polarities one toanother respectively.

The through sections 354 comprises a separate hole 355 having a diametercapable of taking insertion of only the small diameter section, and aninsert-withdraw hole 356 adjacent to the separate hole 355, capable ofmoving the tip to and from the separate hole 355 horizontally andcapable of taking insertion of the larger diameter section of the tip,in a manner forming a pair with the separate hole 355.

As shown in FIG. 18(e), the separate hole 355 penetrates the magneticplates 353 a, 353 b and a pair of projections 364 a, 364 b made ofmagnetic material. The projections 364 a, 364 b project toward thefacing surface of the magnetic plates 353 a, 353 b vertically and areformed so as to be capable of taking insertion of the small diametersection of the tip 321. Each wall part of the projections 364 a 364 bhave opposite polarities by magnetization and correspond to the dividedparts of the nozzle outer members.

Since the through sections 354 according to the present embodiment cantake insertion of the larger diameter section, the through sections 354are formed so as to be larger than the usual through sections 17, 37,57, 77, 97 or the through sections 331 according to the fifteenthembodiment, and this results in occupying two portions of the usualthrough section.

Therefore, all the liquid containing parts in a standard 96well-microplate 361 which is ordinarily used, cannot be available. Asshown by black circles in FIG. 18(c), only 48 liquid containing parts363, being half of all of the liquid containing parts, can be available.The utilized range 352 a of the magnetic force device 353 and thenozzles 351 is shown. The present embodiment enables all the liquidcontaining parts of the 96 well-microplate 361 to be utilized, byenabling the remaining 48 liquid containing parts, being half of all ofthe liquid containing parts (refer to the white circles in FIG. 18(c)),to be utilized. This is done by utilizing 54 through sections, and 54nozzles, in a range of through sections 354 of the magnetic force device353 and a range 352 b of the nozzles.

In order to utilize these 54 sets of nozzles and through sections 354,tip racks 357, 358 are prepared as shown in FIGS. 18(a), (b). Theholding places for the tips in the tip racks 357, 358 are differentaccording to the utilized range 352 a, 352 b of the nozzles. In thiscase, relief holes 359 capable of preventing the nozzles which do notfall within the utilized range 352 a, 353 b of the nozzles fromcollision with the racks 357, 358, are provided on both sides of the 48holes for holding the pipette tips.

Here, the projections of each through section may have a structure shownnot only in FIG. 18(e) but also for example in FIGS. 17(d)(e) (thoughthe diameter of the insert-withdraw hole of this case is larger than thecase of FIGS. 17 (d)(e)).

With the present embodiment, since the tips having a small diametersection and a larger diameter section can be completely withdrawn fromthe through sections of the magnetic force device 353 upward ordownward, fitting and detaching the pipette tips can be easily executed.

With the present embodiment, cross contamination generated bycontaminating the through sections of the magnetic force device with theliquid adhering to the periphery of the pipette tips can be surelyavoided while detaching used pipette tips which have been inserted intothe vessels, or fitting new pipette tips.

Further, with the embodiment, since all of the liquid containing partsmounted in the 96 well-microplate 361 can be available, efficiency ofusage of the vessel is high.

SEVENTEENTH EMBODIMENT

Next, a magnetic force device according to a seventeenth embodiment isdescribed on the basis of FIG. 19.

Since the magnetic force device 370 according to the present embodimentis particularly effective when the nozzles thereof have pipette tipscomprising a small diameter section 375 and a larger diameter section376 capable of being mounted and detached, the following descriptions ofthe present embodiment are devoted to this case.

The magnetic force device 370 comprises a plank member 377 made ofmagnetic material and magnetically connected,to an electromagnet (orpermanent magnet) which comprises a horseshoe-like magnetic element 378wound by a coil 371 near the center thereof, and serving as a magneticsource. The plank member 377 is divided into plural column-like members372, 373 separated in such a manner that the intervals between theneighboring column-like members 372, 373 can take the insertion of thelarger diameter section 376 of the nozzle. Plural protrusions 374 madeof magnetic material project from each column-like member 372, 373 atpredetermined intervals facing one an other in a lateral direction ofthe rows. The facing protrusions themselves are magnetized in a mannerso as to have opposite polarities one to another respectively, and areapart from one another with an interval capable of taking insertion ofonly the small diameter section 375 of each nozzle. Neighboringprotrusions 374 mounted in each column-like member 372, 374 are apartfrom each other so that the larger diameter section 376 can be insertedbetween the protrusions 374. Tips of the opposite protrusions 374correspond to the divided wall parts.

With the present embodiment, the tips can be mounted and dismounted insuch a manner that the magnetic force device is not contaminated by theliquid adhering to the periphery of the pipette tip and the periphery ofthe pipette tip is not contaminated by the liquid adhering to themagnetic force device. Consequently, with the present embodiment, crosscontamination can be completely avoided in spite of the simplestructure.

EIGHTEENTH EMBODIMENT

An apparatus 380 according to an eighteenth embodiment is described onthe basis of FIG. 20. The apparatus utilizes a magnetic force device 316comprising a magnetic source 317.

The apparatus 380 draws and discharges liquid accommodated in a vessel381 (a microplate having 8 rows×12 columns in this example) placed underthe apparatus 380 and having plural liquid containing parts (wells).

The apparatus 380 comprises a sliding body 384 with projecting pluralplungers (96 plungers arranged in a matrix of 8 rows×12 columns, in thisexample), a reservoir body 383 having plural cylindrical reservoirs 382(96 reservoirs arranged in a matrix of 8 rows×12 columns, in thisexample) capable of vertically sliding of the plunger therethrough,plural (96) pipette tips 321 fitted to the lower part of the reservoir382, and arranged in a matrix (8 rows×12 columns) in a way that thepipette tips 321 can be detached. In the embodiment, the pipette tips321 are inserted into each of the through sections of the magnetic forcedevice 316, and the lower ends of the pipette tips 321 reach to belowthe lower magnetic plate by penetrating through the through holes.

The upper part of the sliding body 384 is connected to the lower end ofa ball screw 385. The ball screw 385 engages with a nut part 386. Thenut part 386 is driven to rotate through a belt 387 by a stepping motor388. The ball screw 385 moves vertically by rotation of the nut part386. The reservoir body 383, the magnetic force device 316, and thestepping motor 388 are fixed to a vertical transfer body 389. Thesliding body 384 is supported in the vertical transfer body 389 by atranslation bearing 390 and a rail 391 laid vertically and guiding thetranslation bearing 390. Mechanisms such as the reservoir 382, thereservoir body 383, the sliding body 384, the ball screw 385, and thestepping motor 388 constitute the drawing/discharging device.

The vertical transfer body 389 is supported in a back and forth transferbody 392 through a translation bearing 393 and a rail 394 laidvertically and guiding the translation bearing 393 in a way that thevertical transfer body 389 can vertically transfer to and from the backand forth transfer body 392.

The back and forth transfer body 392 comprises a ball screw 396 and astepping motor 398 driving to rotate the ball screw 396 through acoupler 397. The ball screw 396 engages with a nut part 395 andvertically moves the nut part 395 and the vertical transfer body 389connected to the nut part 395, by the rotation of the ball screw 396.

Furthermore, the back and forth transfer body 392 can move in back andforth directions, by a translation bearing 402 and a rail 400 laid inthe directions, and guiding the translation bearing 402. The back andforth transfer body 392 is supported by a support 399 mounted with arail 400, and a leg 401.

When the apparatus 380 draws and discharges a liquid from and to thevessel 381 respectively, the apparatus 380 drives the back and forthtransfer body 392 to a position over the vessel 381. Next, the lowerparts of the pipette tips 321 are inserted into the vessel 381 byvertical transfer of the vertical transfer body 389. Next, a liquid isdrawn from or discharged to the vessel 381, by moving the sliding body384. On this occasion, only a gas, ordinarily air, is drawn to ordischarged from the reservoirs 382, and a liquid is drawn to ordischarged from the pipette tips 321. Consequently, since the reservoirs382 do not come in contact with the liquid, the reservoirs 382 are notcontaminated by the liquid. The magnetic particles suspended in theliquid adhere to the inner walls of the pipette tips 32 and areseparated, or the magnetic particles separated by adhesion to the innerwalls of the pipette tips 32 can be resuspended in the liquid bycontrolling the magnetic force device 316.

The embodiments above have been described in detail to further explainthe invention, but in no way preclude other embodiments. Consequently,the embodiments can be altered provided the gist of the invention isretained. For example, the elements of the structure such as themagnetic force device and the nozzle, and the drawing/discharging deviceof the apparatus can be arbitrarily combined together while executingnecessary alterations, and can constitute another apparatus for anintegrated process. Further, in the above description, though the methodof generating the magnetic field by the magnetic force device is mainlyby using an electromagnet, this may also be achieved by a permanentmagnet. In this case, the magnetization of the magnetic member isembodied in such a manner that each plate or edge part of the magneticmember comes in contact with or approaches to each magnetic pole of themagnet by rotating the magnet about the axis of the rotation, through90° and 270° with a vertical axis from an initial position, anddemagnetization is embodied in such a manner that each plate or edgepart of the magnetic member is taken away from the magnetic pole by forexample rotating the magnet toward the initial position. Further, in theembodiments above, it is described that the nozzles and the magneticforce device are formed to be separate. However, the nozzles per se maybe included in the magnetic force device, and may be magnetized anddemagnetized.

Thus, in the embodiments above, the above objects of the invention areachieved by adopting a method of arranging magnetization in a plane-likestate, a method of drawing and discharging all together, and a method ofdetecting optically all together.

Further, in the embodiments above, though the reservoirs are describedas being provided in the block-like reservoir body, the reservoir bodymay be an aggregation of bundled cylindrical reservoirs.

Further, in the embodiments above, though leakage of liquid is describedas being prevented by using O-rings, it may be prevented by using rubberpackings provided on the inner wall of the plunger or cylinder, or acombination of rubber packings with O-rings.

Furthermore, in the embodiments above, though it is described that themagnetic force device applies a magnetic force to or removes themagnetic force from each nozzle, this may be applied to or removed fromeach liquid containing part or each column of the column cluster. Theinternal diameter of the through section of the magnetic force device isdetermined on the basis of the diameter of each nozzle, liquidcontaining part or column. In each embodiment, the magnetic force devicemay be mounted as the magnetic apparatus on the integrated apparatus, ina way that it can be dismounted therefrom.

Furthermore, it is needless to say that the number and the arrangementof the nozzles, the through sections and the liquid containing parts areinterpreted as examples only, and are not interpreted as limitations.

What is claimed is:
 1. An apparatus for an integrated process ofmagnetic particles comprising: a drawing/discharging device for drawingand discharging a fluid; plural nozzles arranged in a plane-like stateand passing the fluid therethrough while drawing and discharging; and amagnetic force device for applying and removing a magnetic field to andfrom the nozzles respectively in a manner that the neighborhood of eachnozzle exterior remains stationary; wherein said magnetic force devicecan apply and remove the magnetic force to and from said nozzlesrespectively by enabling magnetization and demagnetization in a nozzleouter member brought in contact with or being near the outer surface ofsaid nozzle or at least a part of said nozzle, in a manner that theneighborhood of each nozzle exterior remains stationary; wherein saidmagnetic force device comprises a magnetic member made of a magneticmaterial and provided with a plurality of through sections arranged in aplane-like state and capable of taking insertion of nozzles; whereinsaid nozzle outer member is a wall of said through sections; and whereineach through section of said magnetic force device comprises a separatehole in which the nozzle is inserted in a way that the outer surface ofthe nozzle can come in contact with or approach to the nozzle outermember, and an insert-withdraw hole mounted adjacent to the separatehole and having an opening larger than that of the separate hole so thatthe nozzle can horizontally move to and from the separate hole and canbe withdrawn and inserted at the insert-withdraw hole.
 2. An apparatusfor an integrated process of magnetic particles according to claim 1,wherein said nozzle comprises a small diameter section and a largerdiameter section, said separate hole has an opening that only the smalldiameter section can be inserted in, and said insert-withdraw hole hasan opening that the larger diameter section can be inserted in.
 3. Anapparatus for an integrated process of magnetic particles according toclaim 1, wherein said nozzle outer member of the magnetic force deviceor a part of said nozzle comprises first and second parts that arespaced from one another in a manner so that the first and second partshave mutually opposite magnetic polarities.
 4. An apparatus for anintegrated process of magnetic particles according to claim 3, whereinsaid magnetic force device comprises a magnetic source having anelectromagnet or a permanent magnet, the magnetic member comprising twomagnetic plates made of magnetic material and connecting with theelectromagnet or capable of connecting with the permanent magnet andcapable of being magnetized and demagnetized, and mounted inface-to-face relationship in spaced positions, the plural throughsections being arranged in a plane-like state, penetrating the twomagnetic plates and being capable of taking insertion of the nozzles,and each nozzle outer member comprising a pair of projections mounted ineach through section, projecting toward the opposite surface of eachmagnetic plate and made of magnetic materials, each projectioncorresponding to one of the first and second parts and the projectionsof each pair being spaced from one another in such a manner that theyhave mutually opposite polarities by magnetization.
 5. An apparatus foran integrated process of magnetic particles according to claim 4,wherein said through sections comprise through holes penetrating throughthe magnetic plates and capable of taking insertion therethrough by thenozzles, and each wall part of the mutually separated through holes hasopposite polarity respectively.
 6. An apparatus for an integratedprocess of magnetic particles according to claim 4, wherein saidmagnetic force device comprises one or more of the magnetic sources,each magnetic source comprises a coil and a magnetic element providedwith the coil, and one end of said magnetic element is connected withone of the two magnetic plates and the other end thereof is connectedwith the other of the two magnetic plates.
 7. An apparatus for anintegrated process of magnetic particles according to claim 6, whereinsaid magnetic elements are mounted outside of the space which is formedby the magnetic plates.
 8. An apparatus for an integrated process ofmagnetic particles according to claim 7, wherein said magnetic elementscomprise a third part and a fourth part which are separately mounted,wherein one end of the third part connects with one of the two magneticplates, the other end of the fourth part connects with the othermagnetic plate, wherein the third part and the fourth part areoverlapped and are wound by wire of a coil, or the other end of thethird part and one part of the fourth part are connected with each endof a fifth part and wound by wire of the coil and made of magneticmaterial.
 9. An apparatus for an integrated process of magneticparticles according to claim 3, wherein the first and second parts aretapered toward a gap.
 10. An apparatus for an integrated process ofmagnetic particles according to claim 4, wherein said pair ofprojections each project from the opening edge of the through section ofone of the magnetic plates toward the other magnetic plate in adirection of insertion of the nozzle in respective directions oppositeto one another, and each tip of the projections is spaced from theopposite surface by a first interval, and the tips of the projectionsare spaced from one another by a second interval shorter than the firstinterval, in such a manner that the tips have opposite polarities,respectively.
 11. An apparatus for an integrated process of magneticparticles according to claim 1, wherein said magnetic force devicecomprises plural magnetic sources, and plural segments defined so as toinclude the area spatially near each magnetic source, respectively. 12.An apparatus for an integrated process of magnetic particles accordingto claim 1, wherein said magnetic force device comprises a magneticsource having a permanent magnet or an electromagnet, and a member madeof magnetic material and magnetically connected to the electromagnet orcapable of magnetically connecting to the permanent magnet, wherein thethrough sections are provided in the member and are capable of takinginsertion of the nozzles.
 13. An apparatus for an integrated process ofmagnetic particles according to claim 12, wherein the through holes ofthe magnetic force device comprise divided wall parts divided in thedirection of the insertion of the nozzle in such a manner that dividedwall parts are apart from one another and have opposite polarities bymagnetization.
 14. An apparatus for an integrated process of magneticparticles according to claim 13, wherein the nozzles comprise a largerdiameter section and a small diameter section, and the member of themagnetic force device comprises plural column members arranged apartfrom each other at intervals capable of taking insertion of the largerdiameter section of the nozzle, and plural protrusions made of magneticmaterial that are projected oppositely from each column member,magnetized in a manner that has opposite polarity to each other andarranged apart from each other at intervals capable of taking insertionof the smaller diameter section of the nozzle, and are arranged alongthe column member at intervals capable of taking insertion of the largerdiameter section of the nozzle, wherein opposite pointed ends of theprotrusions correspond with the divided wall parts.
 15. An apparatus foran integrated process of magnetic particles according to claim 1,wherein said nozzles comprise small diameter pipes communicating withthe through sections of the magnetic member and capable of beinginserted into a vessel.
 16. An apparatus for an integrated process ofmagnetic particles according to claim 1, wherein saiddrawing/discharging device comprises a reservoir body comprising pluralreservoirs arranged in a plane-like state for storing a drawn fluid andcommunicating with the nozzles, and an increasing/decreasing device forincreasing and decreasing pressure within the reservoirs and the nozzlesin a manner that draws or discharges the fluid.
 17. An apparatus for anintegrated process of magnetic particles according to claim 16, whereinsaid increasing/decreasing device comprises a sliding body capable ofmoving vertically to and from the reservoir body, and slidingprojections arranged in a plane-like state, projecting downward from thesliding body and capable of sliding through the nozzles in such a mannerthat the pressure within the reservoirs or nozzles increases ordecreases.
 18. An apparatus for an integrated process of magneticparticles according to claim 17, wherein said sliding projections areformed to have a two-step structure comprising a larger diameter sectioncapable of sliding through the reservoir, and a smaller diameter sectioncapable of extending along the axes of the larger diameter section andsliding through the nozzle communicating with the reservoir.
 19. Anapparatus for an integrated process of magnetic particles according toclaim 16, wherein said nozzles comprise a tip capable of being mountedto and dismounted from the drawing/discharging device.
 20. An apparatusfor an integrated process of magnetic particles according to claim 19,comprising a pushing body having pushing pipes inserted from the upperside of the reservoirs into the reservoirs and capable of pushing thenozzles out of the reservoirs, wherein the nozzles are detachablymounted to the reservoirs while being inserted from the lower side ofthe reservoirs, and the increasing/decreasing device comprises a slidingbody having plural sliding projections projecting downward, capable ofsliding through the pushing pipes and capable of moving vertically toand from the reservoirs respectively, in a manner that the pressurewithin the reservoirs or nozzles can be increased or decreased.
 21. Anapparatus for an integrated process of magnetic particles according toclaim 19, wherein said nozzles are detachably mounted to the lower partof the reservoirs and are inserted to a predetermined depth in thereservoirs, sliding projections can slide to a depth of the installationdepth of the nozzles in the reservoirs, and a projecting lip part isprojected from the outer side of the nozzles exposed under the magneticforce device for mounting and dismounting, and a stroke-down plateprovided with plural small hole parts with respective diameters largerthan that of the nozzles and smaller than that of the lip parts ismounted between the magnetic force device and the lip parts in a waythat the hole parts take insertion of the nozzles and the nozzles can bedetached by moving the stroke-down plate down.
 22. An apparatus for anintegrated process of magnetic particles according to claim 17, whereinan inner wall of the upper part of said reservoir is formed to becylindrical, and that of the lower part of said reservoir is formed tobe funnel-shaped and is connected with said nozzles.
 23. An apparatusfor an integrated process of magnetic particles according to claim 16,wherein a cleaning liquid can be poured into each reservoir from apassage mounted in the top or side of the reservoir body.
 24. Anapparatus for an integrated process of magnetic particles according toclaim 1, comprising a light measuring device for receiving light fromall the vessels or plural liquid containing parts arranged in aplane-like state, simultaneously or all together and measuring thestrength of the light or processing it as an image in order to measure astate of light emission.
 25. An apparatus for an integrated process ofmagnetic particles according to claim 24, wherein the light measuringdevice comprises plural receiving components arranged in a plane-likestate, mounted at places corresponding to the liquid containing partsand having the same number as that of the liquid containing part, andshading fences mounted between neighboring receiving components forpreventing light entering to other than the corresponding liquidcontaining part.
 26. An apparatus for an integrated process of magneticparticles, comprising: a drawing/discharging device for drawing anddischarging a fluid; plural nozzles arranged in a plane-like state andpassing the fluid there through while drawing and discharging; amagnetic force device for applying and removing a magnetic field to andfrom the nozzles respectively in a manner that the neighborhood of eachnozzle exterior remains stationary, wherein said magnetic force devicecomprises an insulating device for preventing heat generated bymagnetization or generation of a magnetic field from being transmittedtoward the nozzle; and a ventilator for sending air to the magneticforce device or the neighborhood thereof.
 27. An apparatus comprising: aplurality of nozzles for passing fluid; and a magnetic field generatorwhich can generate a magnetic field that is effective within thenozzles, the magnetic field generator comprising a part which has: aplurality of first openings for receiving the nozzles; and a pluralityof second openings which are larger than and are each disposed adjacentto and communicate with a respective one of the first openings, so thatthe nozzles can each be inserted into and withdrawn from a respectiveone of the second openings, and can each be moved between one of thefirst openings and the second opening which communicates therewith. 28.An apparatus according to claim 27, further comprising a fluid flowportion cooperable with the nozzles for effecting fluid flow through thenozzles.
 29. An apparatus according to claim 28, wherein each of thenozzles has therethrough a fluid flow opening, and the fluid flowportion has a plurality of movable projections which are each slidablewithin the fluid flow opening of a respective nozzle.
 30. An apparatusaccording to claim 27, wherein the magnetic field generator has one of apermanent magnet and an electromagnetic, which is coupled to the part ofthe magnetic field generator.
 31. An apparatus according to claim 30,wherein the part of the magnetic field generator has two spaced plateswhich are each coupled to the one of the permanent magnet and theelectromagnetic in a manner so that the plates have opposite magneticpolarities when the magnetic field generator is generating a magneticfield, each of the two plates having the first and second openingsextending therethrough.
 32. An apparatus according to claim 27, whereinthe part of the magnetic field generator member has, adjacent each ofthe first openings therein, a pair of portions which are spaced, andwhich have opposite magnetic polarities when the magnetic fieldgenerator is generating a magnetic field.
 33. An apparatus according toclaim 32, wherein the part of the magnetic field generator has twospaced plates which have opposite magnetic polarities when the magneticfield generator is generating a magnetic field, which each have thefirst and second openings extending therethrough, and which each have aplurality of projections extending toward the other thereof, theportions of each pair being two of the projections that are eachprovided on a respective plate.
 34. An apparatus according to claim 33,wherein the projections on each plate have an end which is spaced fromthe other plate by a first distance, and wherein the ends of theprojections of each pair are spaced from each other by a second distanceless than the first distance.
 35. An apparatus according to claim 27,wherein the part of the magnetic field generator has a plurality ofspaced and approximately parallel column portions, and each columnportion has along each side thereof a plurality of spaced protrusionswhich each project toward one of the protrusions on an adjacent columnportion, each of the first openings being a region between ends of arespective pair of the protrusions, each of the second openings being aregion between two column portions which is offset from the protrusionson the column portions, and the protrusions of each pair having oppositemagnetic polarities when the magnetic field generator is generating amagnetic field.
 36. An apparatus according to claim 27, furthercomprising a vessel having therein a plurality of holes into which thenozzles can be inserted.
 37. An apparatus according to claim 36, furthercomprising a light measuring portion for receiving light from the vesselin order to measure a state of light emission which is a function ofsubstances in the respective holes of the vessel.